rs971831

chr2-49105231-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.153-36941C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,910 control chromosomes in the GnomAD database, including 10,820 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 0.37 (10820 hom., cov: 31)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSHR	NM_000145.4	c.153-36941C>T		intron_variant		ENST00000406846.7
FSHR	NM_181446.3	c.153-36941C>T		intron_variant
FSHR	XM_011532733.3	c.153-36941C>T		intron_variant
FSHR	XM_011532740.1	c.153-36941C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSHR	ENST00000406846.7	c.153-36941C>T		intron_variant		1	NM_000145.4	P1
	ENST00000634588.1	n.492+158826G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55988 AN: 151790 Hom.: 10802 Cov.: 31

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.369 AC: 56048 AN: 151910 Hom.: 10820 Cov.: 31 AF XY: 0.372 AC XY: 27605 AN XY: 74234

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.369

Alfa AF: 0.323 Hom.: 15614

Bravo AF: 0.382

Asia WGS AF: 0.449 AC: 1561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.8
Dann	Benign	0.75

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: rs971831; hg19: chr2-49332370;