chr2-49154446-C-T

Position:

chr2-49154446-C-T

Variant summary

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

The ENST00000406846.7(FSHR):c.-29G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,609,736 control chromosomes in the GnomAD database, including 70,533 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6505 hom., cov: 31)

Exomes 𝑓: 0.29 ( 64028 hom. )

Consequence

FSHR
ENST00000406846.7 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.730

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:

(HGNC:):

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=-0.5).

BP6

Variant 2-49154446-C-T is Benign according to our data. Variant chr2-49154446-C-T is described in ClinVar as [Benign]. Clinvar id is 137403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
FSHR	NM_000145.4 linkuse as main transcript	c.-29G>A	5_prime_UTR_variant	1/10	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3 linkuse as main transcript	c.-29G>A	5_prime_UTR_variant	1/9		NP_852111.2
FSHR	XM_011532733.3 linkuse as main transcript	c.-29G>A	5_prime_UTR_variant	1/11		XP_011531035.1
FSHR	XM_011532740.1 linkuse as main transcript	c.-29G>A	5_prime_UTR_variant	1/11		XP_011531042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7 linkuse as main transcript	c.-29G>A		5_prime_UTR_variant	1/10	1	NM_000145.4	ENSP00000384708	P1
	ENST00000634588.1 linkuse as main transcript	n.492+208041C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.286

AC:

43353

AN:

151800

Hom.:

6493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.225

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.351

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.286

GnomAD3 exomes

AF:

0.322

AC:

80116

AN:

249064

Hom.:

14134

AF XY:

0.315

AC XY:

42448

AN XY:

134620

show subpopulations

Gnomad AFR exome

AF:

0.256

Gnomad AMR exome

AF:

0.489

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.478

Gnomad SAS exome

AF:

0.341

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.290

AC:

422620

AN:

1457818

Hom.:

64028

Cov.:

AF XY:

0.291

AC XY:

210771

AN XY:

725280

show subpopulations

Gnomad4 AFR exome

AF:

0.248

Gnomad4 AMR exome

AF:

0.473

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.480

Gnomad4 SAS exome

AF:

0.342

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.276

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.286

AC:

43405

AN:

151918

Hom.:

6505

Cov.:

AF XY:

0.288

AC XY:

21363

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.252

Gnomad4 AMR

AF:

0.370

Gnomad4 ASJ

AF:

0.225

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.349

Gnomad4 FIN

AF:

0.271

Gnomad4 NFE

AF:

0.275

Gnomad4 OTH

AF:

0.286

Alfa

AF:

0.269

Hom.:

5540

Bravo

AF:

0.294

Asia WGS

AF:

0.423

AC:

1467

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 20, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Ovarian dysgenesis 1

Benign:1

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. -

Ovarian hyperstimulation syndrome

Benign:1

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.89

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