rs1007541

chr2-48981895-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.668+1017G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,100 control chromosomes in the GnomAD database, including 2,135 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 0.16 (2135 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSHR	NM_000145.4	c.668+1017G>A		intron_variant		ENST00000406846.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSHR	ENST00000406846.7	c.668+1017G>A		intron_variant		1	NM_000145.4	P1
	ENST00000634588.1	n.492+35490C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23920 AN: 151982 Hom.: 2129 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.158 AC: 23958 AN: 152100 Hom.: 2135 Cov.: 32 AF XY: 0.159 AC XY: 11836 AN XY: 74362

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.0972

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.157

Alfa AF: 0.129 Hom.: 1385

Bravo AF: 0.167

Asia WGS AF: 0.180 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	4.9
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: rs1007541; hg19: chr2-49209034;