rs6545094

Positions:

• chr2-49039175-G-A

Variant summary

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

The NM_000145.4(FSHR):​c.225-19015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,992 control chromosomes in the GnomAD database, including 12,687 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 0.41 (12687 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSHR	NM_000145.4	c.225-19015C>T		intron_variant		ENST00000406846.7
FSHR	NM_181446.3	c.225-19015C>T		intron_variant
FSHR	XM_011532733.3	c.225-19015C>T		intron_variant
FSHR	XM_011532740.1	c.225-19015C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSHR	ENST00000406846.7	c.225-19015C>T		intron_variant		1	NM_000145.4	P1
	ENST00000634588.1	n.492+92770G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61587 AN: 151874 Hom.: 12683 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.405 AC: 61622 AN: 151992 Hom.: 12687 Cov.: 32 AF XY: 0.405 AC XY: 30076 AN XY: 74294

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.394

Alfa AF: 0.413 Hom.: 18142

Bravo AF: 0.403

Asia WGS AF: 0.427 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.21

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: rs6545094; hg19: chr2-49266314;