rs3913665

Positions:

• chr2-49049103-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000406846.7(FSHR):​c.224+19116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,602 control chromosomes in the GnomAD database, including 24,217 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 0.56 (24217 hom., cov: 30)
• Consequence: FSHR ENST00000406846.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSHR	NM_000145.4	c.224+19116T>C		intron_variant		ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.224+19116T>C		intron_variant			NP_852111.2
FSHR	XM_011532733.3	c.224+19116T>C		intron_variant			XP_011531035.1
FSHR	XM_011532740.1	c.224+19116T>C		intron_variant			XP_011531042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.224+19116T>C		intron_variant		1	NM_000145.4	ENSP00000384708	P1
	ENST00000634588.1	n.492+102698A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84193 AN: 151484 Hom.: 24194 Cov.: 30

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.556 AC: 84262 AN: 151602 Hom.: 24217 Cov.: 30 AF XY: 0.558 AC XY: 41290 AN XY: 74036

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.598

Alfa AF: 0.591 Hom.: 34753

Bravo AF: 0.555

Asia WGS AF: 0.664 AC: 2308 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs3913665; hg19: chr2-49276242;