chrX-147925702-T-A

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.198+69T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 702,548 control chromosomes in the GnomAD database, including 5,214 homozygotes. There are 22,042 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 688 hom., 2698 hem., cov: 23)

Exomes 𝑓: 0.10 ( 4526 hom. 19344 hem. )

Consequence

FMR1
NM_002024.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.481

Publications

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

new If you want to explore the variant's impact on the transcript NM_002024.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.81).

BP6

Variant X-147925702-T-A is Benign according to our data. Variant chrX-147925702-T-A is described in ClinVar as Benign. ClinVar VariationId is 1179613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002024.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FMR1	NM_002024.6	MANE Select	c.198+69T>A	intron	N/A	NP_002015.1	Q06787-1
FMR1	NM_001185076.2		c.198+69T>A	intron	N/A	NP_001172005.1	Q06787-9
FMR1	NM_001185082.2		c.198+69T>A	intron	N/A	NP_001172011.1	Q06787-8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FMR1	ENST00000370475.9	TSL:1 MANE Select	c.198+69T>A	intron	N/A	ENSP00000359506.5	Q06787-1
FMR1	ENST00000218200.12	TSL:1	c.198+69T>A	intron	N/A	ENSP00000218200.8	Q06787-9
FMR1	ENST00000439526.6	TSL:1	c.198+69T>A	intron	N/A	ENSP00000395923.2	G3V0J0

Frequencies

GnomAD3 genomes

AF:

0.0821

AC:

9141

AN:

111344

Hom.:

690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.0585

Gnomad EAS

AF:

0.568

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0503

Gnomad MID

AF:

0.0630

Gnomad NFE

AF:

0.0652

Gnomad OTH

AF:

0.125

GnomAD4 exome

AF:

0.100

AC:

59107

AN:

591152

Hom.:

4526

AF XY:

0.111

AC XY:

19344

AN XY:

175018

show subpopulations

African (AFR)

AF:

0.0129

AC:

214

AN:

16600

American (AMR)

AF:

0.269

AC:

8828

AN:

32810

Ashkenazi Jewish (ASJ)

AF:

0.0552

AC:

886

AN:

16052

East Asian (EAS)

AF:

0.529

AC:

14354

AN:

27143

South Asian (SAS)

AF:

0.112

AC:

4810

AN:

42970

European-Finnish (FIN)

AF:

0.0618

AC:

2433

AN:

39360

Middle Eastern (MID)

AF:

0.0946

AC:

218

AN:

2305

European-Non Finnish (NFE)

AF:

0.0630

AC:

24231

AN:

384919

Other (OTH)

AF:

0.108

AC:

3133

AN:

28993

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1605

3211

4816

6422

8027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

732

1464

2196

2928

3660

<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:

0.0820

AC:

9139

AN:

111396

Hom.:

688

Cov.:

AF XY:

0.0803

AC XY:

2698

AN XY:

33612

show subpopulations

African (AFR)

AF:

0.0161

AC:

494

AN:

30726

American (AMR)

AF:

0.209

AC:

2184

AN:

10453

Ashkenazi Jewish (ASJ)

AF:

0.0585

AC:

154

AN:

2633

East Asian (EAS)

AF:

0.567

AC:

1946

AN:

3430

South Asian (SAS)

AF:

0.102

AC:

271

AN:

2647

European-Finnish (FIN)

AF:

0.0503

AC:

301

AN:

5990

Middle Eastern (MID)

AF:

0.0642

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0652

AC:

3464

AN:

53098

Other (OTH)

AF:

0.123

AC:

186

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

241

482

723

964

1205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0702

Hom.:

388

Bravo

AF:

0.102

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.65

(source)

DANN

Benign

0.74

PhyloP100

-0.48

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over