Genetic Variant FMR1:c.-108_-100dupCGGCGGCGG (chrX-147912049-C-CGCGGCGGCG) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_002024.6(FMR1):c.-108_-100dupCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 118 hom., 774 hem., cov: 2)

Exomes 𝑓: 0.045 ( 9 hom. 186 hem. )

Failed GnomAD Quality Control

Consequence

FMR1
NM_002024.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.618

Publications

0 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 links:

FMR1-AS1 (HGNC:39081): (FMR1 antisense RNA 1)

FMR1-AS1 links:

ENSG00000274086 (HGNC:):

ENSG00000274086 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant X-147912049-C-CGCGGCGGCG is Benign according to our data. Variant chrX-147912049-C-CGCGGCGGCG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 763962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMR1	NM_002024.6 link	c.-108_-100dupCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 17	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.-108_-100dupCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 17	1	NM_002024.6	ENSP00000359506.5		Q06787-1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

3603

AN:

35043

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0426

Gnomad AMI

AF:

0.0447

Gnomad AMR

AF:

0.0693

Gnomad ASJ

AF:

0.0778

Gnomad EAS

AF:

0.0141

Gnomad SAS

AF:

0.0728

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.0580

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.0989

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0452

AC:

281

AN:

6216

Hom.:

Cov.:

AF XY:

0.0561

AC XY:

186

AN XY:

3316

show subpopulations

African (AFR)

AF:

0.0303

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0313

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0455

AC:

265

AN:

5827

Other (OTH)

AF:

0.0765

AC:

AN:

170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.103

AC:

3605

AN:

35041

Hom.:

118

Cov.:

AF XY:

0.134

AC XY:

774

AN XY:

5795

show subpopulations

African (AFR)

AF:

0.0427

AC:

416

AN:

9734

American (AMR)

AF:

0.0692

AC:

191

AN:

2762

Ashkenazi Jewish (ASJ)

AF:

0.0778

AC:

AN:

823

East Asian (EAS)

AF:

0.0141

AC:

AN:

569

South Asian (SAS)

AF:

0.0729

AC:

AN:

425

European-Finnish (FIN)

AF:

0.181

AC:

151

AN:

832

Middle Eastern (MID)

AF:

0.0690

AC:

AN:

European-Non Finnish (NFE)

AF:

0.140

AC:

2686

AN:

19192

Other (OTH)

AF:

0.0985

AC:

AN:

467

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

191

286

382

477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0247

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.62

Mutation Taster

=265/35

polymorphism

(source)

Splicing

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

Publications

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X-147912049-CGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

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