rs6166

Positions:

chr2-48962782-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000145.4(FSHR):c.2039G>A(p.Ser680Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,613,272 control chromosomes in the GnomAD database, including 252,236 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 24652 hom., cov: 32)

Exomes 𝑓: 0.56 ( 227584 hom. )

Consequence

FSHR
NM_000145.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0530

Variant links:

Genes affected

FSHR (HGNC:3969): (follicle stimulating hormone receptor) The protein encoded by this gene belongs to family 1 of G-protein coupled receptors. It is the receptor for follicle stimulating hormone and functions in gonad development. Mutations in this gene cause ovarian dysgenesis type 1, and also ovarian hyperstimulation syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

FSHR links:

ENSG00000282890 (HGNC:):

ENSG00000282890 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 (MetaRNN=6.0149523E-6).

BP6

Variant 2-48962782-C-T is Benign according to our data. Variant chr2-48962782-C-T is described in ClinVar as [Benign]. Clinvar id is 16247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-48962782-C-T is described in Lovd as [Benign]. Variant chr2-48962782-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSHR	NM_000145.4 linkuse as main transcript	c.2039G>A	p.Ser680Asn	missense_variant	10/10	ENST00000406846.7	NP_000136.2	P23945A0A1D5RMN4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FSHR	ENST00000406846.7 linkuse as main transcript	c.2039G>A	p.Ser680Asn	missense_variant	10/10	1	NM_000145.4	ENSP00000384708.2	A0A1D5RMN4
FSHR	ENST00000304421.8 linkuse as main transcript	c.1961G>A	p.Ser654Asn	missense_variant	9/9	1		ENSP00000306780.4	P23945
ENSG00000282890	ENST00000634588.1 linkuse as main transcript	n.492+16377C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

86242

AN:

151908

Hom.:

24645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.583

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.602

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.680

Gnomad SAS

AF:

0.562

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.551

Gnomad OTH

AF:

0.556

GnomAD3 exomes

AF:

0.574

AC:

144230

AN:

251060

Hom.:

41947

AF XY:

0.569

AC XY:

77131

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.592

Gnomad AMR exome

AF:

0.671

Gnomad ASJ exome

AF:

0.476

Gnomad EAS exome

AF:

0.669

Gnomad SAS exome

AF:

0.546

Gnomad FIN exome

AF:

0.556

Gnomad NFE exome

AF:

0.548

Gnomad OTH exome

AF:

0.566

GnomAD4 exome

AF:

0.557

AC:

813884

AN:

1461246

Hom.:

227584

Cov.:

AF XY:

0.555

AC XY:

403744

AN XY:

726958

show subpopulations

Gnomad4 AFR exome

AF:

0.589

Gnomad4 AMR exome

AF:

0.659

Gnomad4 ASJ exome

AF:

0.471

Gnomad4 EAS exome

AF:

0.656

Gnomad4 SAS exome

AF:

0.542

Gnomad4 FIN exome

AF:

0.555

Gnomad4 NFE exome

AF:

0.552

Gnomad4 OTH exome

AF:

0.559

GnomAD4 genome

AF:

0.568

AC:

86292

AN:

152026

Hom.:

24652

Cov.:

AF XY:

0.567

AC XY:

42132

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.583

Gnomad4 AMR

AF:

0.602

Gnomad4 ASJ

AF:

0.481

Gnomad4 EAS

AF:

0.679

Gnomad4 SAS

AF:

0.561

Gnomad4 FIN

AF:

0.552

Gnomad4 NFE

AF:

0.550

Gnomad4 OTH

AF:

0.554

Alfa

AF:

0.552

Hom.:

57277

Bravo

AF:

0.574

TwinsUK

AF:

0.550

AC:

2040

ALSPAC

AF:

0.551

AC:

2125

ESP6500AA

AF:

0.587

AC:

2588

ESP6500EA

AF:

0.543

AC:

4672

ExAC

AF:

0.573

AC:

69519

Asia WGS

AF:

0.588

AC:

2045

AN:

3478

EpiCase

AF:

0.540

EpiControl

AF:

0.543

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ovarian hyperstimulation syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Benign, no assertion criteria provided	literature only	OMIM	Aug 01, 2005	- -

Ovarian dysgenesis 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 21269619, 19403562, 20399696, 21546300, 23470615, 23139742, 23413141, 16574671, 25132286, 19550076, 20817169, 20514429, 23536150, 24970684, 24718625, 21680247, 18159088, 15886248, 26905078, 29683332, 28282771, 25526787, 28547204) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.29

DANN

Benign

0.18

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.11

T;.

MetaRNN

Benign

0.0000060

T;T

MetaSVM

Benign

-0.92

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.38

N;N

REVEL

Benign

0.033

Sift

Benign

0.97

T;T

Sift4G

Benign

0.71

T;T

Vest4

0.013

MPC

0.023

ClinPred

0.0012

GERP RS

1.5

gMVP

0.30

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