X-147928802-G-A

Position:

chrX-147928802-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002024.6(FMR1):c.414G>A(p.Arg138Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 1,206,186 control chromosomes in the GnomAD database, including 3,659 homozygotes. There are 34,800 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 539 hom., 3151 hem., cov: 23)

Exomes 𝑓: 0.087 ( 3120 hom. 31649 hem. )

Consequence

FMR1
NM_002024.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.27

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 (HGNC:):

FMR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant X-147928802-G-A is Benign according to our data. Variant chrX-147928802-G-A is described in ClinVar as [Benign]. Clinvar id is 94023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-147928802-G-A is described in Lovd as [Benign]. Variant chrX-147928802-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMR1	NM_002024.6 linkuse as main transcript	c.414G>A	p.Arg138Arg	synonymous_variant	5/17	ENST00000370475.9	NP_002015.1	Q06787-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475.9 linkuse as main transcript	c.414G>A	p.Arg138Arg	synonymous_variant	5/17	1	NM_002024.6	ENSP00000359506.5		Q06787-1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

11406

AN:

111212

Hom.:

539

Cov.:

AF XY:

0.0940

AC XY:

3145

AN XY:

33460

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0508

Gnomad ASJ

AF:

0.0470

Gnomad EAS

AF:

0.00112

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.0840

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0867

Gnomad OTH

AF:

0.0980

GnomAD3 exomes

AF:

0.0812

AC:

14853

AN:

182893

Hom.:

534

AF XY:

0.0820

AC XY:

5535

AN XY:

67481

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.0377

Gnomad ASJ exome

AF:

0.0479

Gnomad EAS exome

AF:

0.000289

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.0906

Gnomad NFE exome

AF:

0.0908

Gnomad OTH exome

AF:

0.0765

GnomAD4 exome

AF:

0.0872

AC:

95437

AN:

1094923

Hom.:

3120

Cov.:

AF XY:

0.0877

AC XY:

31649

AN XY:

360693

show subpopulations

Gnomad4 AFR exome

AF:

0.174

Gnomad4 AMR exome

AF:

0.0402

Gnomad4 ASJ exome

AF:

0.0491

Gnomad4 EAS exome

AF:

0.000265

Gnomad4 SAS exome

AF:

0.0985

Gnomad4 FIN exome

AF:

0.0892

Gnomad4 NFE exome

AF:

0.0895

Gnomad4 OTH exome

AF:

0.0867

GnomAD4 genome

AF:

0.103

AC:

11411

AN:

111263

Hom.:

539

Cov.:

AF XY:

0.0940

AC XY:

3151

AN XY:

33521

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.0507

Gnomad4 ASJ

AF:

0.0470

Gnomad4 EAS

AF:

0.00112

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.0840

Gnomad4 NFE

AF:

0.0867

Gnomad4 OTH

AF:

0.100

Alfa

AF:

0.0898

Hom.:

2025

Bravo

AF:

0.105

EpiCase

AF:

0.0968

EpiControl

AF:

0.0946

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 26, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2014

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Fragile X syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Fragile X syndrome;C1839780:Fragile X-associated tremor/ataxia syndrome;C4552079:Premature ovarian failure 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Nov 03, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.2

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over