2-49013003-C-T

Position:

• chr2-49013003-C-T

Variant summary

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

The NM_000145.4(FSHR):​c.374+4486G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,798 control chromosomes in the GnomAD database, including 33,277 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 0.63 (33277 hom., cov: 30)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681

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]

ENSG00000282890 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSHR	NM_000145.4	c.374+4486G>A		intron_variant		ENST00000406846.7	NP_000136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.374+4486G>A		intron_variant		1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96230 AN: 151680 Hom.: 33285 Cov.: 30

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.634 AC: 96245 AN: 151798 Hom.: 33277 Cov.: 30 AF XY: 0.636 AC XY: 47210 AN XY: 74186

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.654

Alfa AF: 0.588 Hom.: 2000

Bravo AF: 0.624

Asia WGS AF: 0.665 AC: 2310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.76
DANN	Benign	0.28

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: rs1316521; hg19: chr2-49240142;