Variant rs25714 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 ClinVar 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 Lovd as [Benign].

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/exons	MANE	Protein	UniProt
FMR1	NM_002024.6 linkuse as main transcript	c.990+14C>T		intron_variant		ENST00000370475.9	NP_002015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475.9 linkuse as main transcript	c.990+14C>T		intron_variant		1	NM_002024.6	ENSP00000359506	P3	Q06787-1

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

13402

AN:

110776

Hom.:

1088

Cov.:

AF XY:

0.121

AC XY:

3997

AN XY:

33078

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

GnomAD3 exomes

AF:

0.161

AC:

29106

AN:

181043

Hom.:

3566

AF XY:

0.144

AC XY:

9501

AN XY:

65759

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 SAS exome

AF:

0.138

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

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.273

Gnomad4 ASJ exome

AF:

0.0589

Gnomad4 EAS exome

AF:

0.640

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.0655

Gnomad4 NFE exome

AF:

0.0673

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.121

AC:

13402

AN:

110827

Hom.:

1085

Cov.:

AF XY:

0.121

AC XY:

3999

AN XY:

33139

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.230

Gnomad4 ASJ

AF:

0.0599

Gnomad4 EAS

AF:

0.705

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.0544

Gnomad4 NFE

AF:

0.0674

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.0807

Hom.:

2330

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

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 29, 2017	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Fragile X syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Apr 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

DANN

Benign

0.38

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