rs4971884

Positions:

• chr2-49112209-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.152+42057C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,084 control chromosomes in the GnomAD database, including 4,269 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 0.22 (4269 hom., cov: 33)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSHR	NM_000145.4	c.152+42057C>T		intron_variant		ENST00000406846.7
FSHR	NM_181446.3	c.152+42057C>T		intron_variant
FSHR	XM_011532733.3	c.152+42057C>T		intron_variant
FSHR	XM_011532740.1	c.152+42057C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSHR	ENST00000406846.7	c.152+42057C>T		intron_variant		1	NM_000145.4	P1
	ENST00000634588.1	n.492+165804G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32687 AN: 151966 Hom.: 4263 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.215 AC: 32706 AN: 152084 Hom.: 4269 Cov.: 33 AF XY: 0.221 AC XY: 16462 AN XY: 74348

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.226

Alfa AF: 0.215 Hom.: 522

Bravo AF: 0.220

Asia WGS AF: 0.394 AC: 1367 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.84
DANN	Benign	0.45

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: rs4971884; hg19: chr2-49339348;