rs11692782

Variant names:

• chr2-49064754-T-A
• rs11692782
• NM_000145.4:c.224+3465A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000145.4(FSHR):​c.224+3465A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,890 control chromosomes in the GnomAD database, including 12,760 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12760 hom., cov: 31)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• ovarian hyperstimulation syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• ovarian dysgenesis 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• 46 XX gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000282890 (HGNC:58158):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.224+3465A>T		intron_variant	Intron 2 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.224+3465A>T		intron_variant	Intron 2 of 8		NP_852111.2
FSHR	XM_011532733.3	c.224+3465A>T		intron_variant	Intron 2 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.224+3465A>T		intron_variant	Intron 2 of 10		XP_011531042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.224+3465A>T		intron_variant	Intron 2 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60997 AN: 151772 Hom.: 12751 Cov.: 31

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.438

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.402 AC: 61041 AN: 151890 Hom.: 12760 Cov.: 31 AF XY: 0.403 AC XY: 29901 AN XY: 74230

African (AFR) AF: 0.281 AC: 11636 AN: 41428

American (AMR) AF: 0.445 AC: 6773 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1571 AN: 3470

East Asian (EAS) AF: 0.537 AC: 2763 AN: 5144

South Asian (SAS) AF: 0.496 AC: 2390 AN: 4814

European-Finnish (FIN) AF: 0.373 AC: 3931 AN: 10548

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30493 AN: 67938

Other (OTH) AF: 0.437 AC: 923 AN: 2110

Alfa AF: 0.407 Hom.: 1600

Bravo AF: 0.401

Asia WGS AF: 0.497 AC: 1727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.0
DANN	Benign	0.75
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11692782; hg19: chr2-49291893;