NM_002024.6:c.990+14C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002024.6(FMR1):c.990+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,016,839 control chromosomes in the GnomAD database, including 8,332 homozygotes. There are 32,742 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1085 hom., 3999 hem., cov: 23)

Exomes 𝑓: 0.10 ( 7247 hom. 28743 hem. )

Consequence

FMR1
NM_002024.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.190

Publications

16 publications found

Variant links:

Genes affected

FMR1 (HGNC:3775): (fragile X messenger ribonucleoprotein 1) The protein encoded by this gene binds RNA and is associated with polysomes. The encoded protein may be involved in mRNA trafficking from the nucleus to the cytoplasm. A trinucleotide repeat (CGG) in the 5' UTR is normally found at 6-53 copies, but an expansion to 55-230 repeats is the cause of fragile X syndrome. Expansion of the trinucleotide repeat may also cause one form of premature ovarian failure (POF1). Multiple alternatively spliced transcript variants that encode different protein isoforms and which are located in different cellular locations have been described for this gene. [provided by RefSeq, May 2010]

FMR1 Gene-Disease associations (from GenCC):

fragile X syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
fragile X-associated tremor/ataxia syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
premature ovarian failure 1
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
symptomatic form of fragile X syndrome in female carrier
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

FMR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-147936627-C-T is Benign according to our data. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147936627-C-T is described in CliVar as Benign. Clinvar id is 94025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMR1	NM_002024.6 link	c.990+14C>T		intron_variant	Intron 10 of 16	ENST00000370475.9	NP_002015.1	Q06787-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475.9 link	c.990+14C>T		intron_variant	Intron 10 of 16	1	NM_002024.6	ENSP00000359506.5		Q06787-1

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

13402

AN:

110776

Hom.:

1088

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.705

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.0544

Gnomad MID

AF:

0.0678

Gnomad NFE

AF:

0.0674

Gnomad OTH

AF:

0.160

GnomAD2 exomes

AF:

0.161

AC:

29106

AN:

181043

AF XY:

0.144

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.277

Gnomad ASJ exome

AF:

0.0644

Gnomad EAS exome

AF:

0.714

Gnomad FIN exome

AF:

0.0646

Gnomad NFE exome

AF:

0.0684

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.102

AC:

92357

AN:

906012

Hom.:

7247

Cov.:

AF XY:

0.114

AC XY:

28743

AN XY:

253082

show subpopulations

African (AFR)

AF:

0.126

AC:

2882

AN:

22787

American (AMR)

AF:

0.273

AC:

9503

AN:

34850

Ashkenazi Jewish (ASJ)

AF:

0.0589

AC:

1069

AN:

18157

East Asian (EAS)

AF:

0.640

AC:

18821

AN:

29399

South Asian (SAS)

AF:

0.140

AC:

6998

AN:

50007

European-Finnish (FIN)

AF:

0.0655

AC:

2648

AN:

40405

Middle Eastern (MID)

AF:

0.120

AC:

451

AN:

3752

European-Non Finnish (NFE)

AF:

0.0673

AC:

44892

AN:

666847

Other (OTH)

AF:

0.128

AC:

5093

AN:

39808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

2299

4597

6896

9194

11493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1894

3788

5682

7576

9470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.121

AC:

13402

AN:

110827

Hom.:

1085

Cov.:

AF XY:

0.121

AC XY:

3999

AN XY:

33139

show subpopulations

African (AFR)

AF:

0.123

AC:

3740

AN:

30459

American (AMR)

AF:

0.230

AC:

2403

AN:

10460

Ashkenazi Jewish (ASJ)

AF:

0.0599

AC:

158

AN:

2636

East Asian (EAS)

AF:

0.705

AC:

2456

AN:

3483

South Asian (SAS)

AF:

0.145

AC:

386

AN:

2669

European-Finnish (FIN)

AF:

0.0544

AC:

321

AN:

5903

Middle Eastern (MID)

AF:

0.0657

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.0674

AC:

3562

AN:

52816

Other (OTH)

AF:

0.157

AC:

236

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

374

749

1123

1498

1872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0837

Hom.:

2835

Bravo

AF:

0.143

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 29, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jun 18, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Fragile X syndrome

Benign:1

Apr 12, 2018

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

(source)

DANN

Benign

0.38

PhyloP100

0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over