2-49123858-G-A

Position:

• chr2-49123858-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+30408C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,910 control chromosomes in the GnomAD database, including 5,007 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 0.25 (5007 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSHR	NM_000145.4	c.152+30408C>T		intron_variant		ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.152+30408C>T		intron_variant			NP_852111.2
FSHR	XM_011532733.3	c.152+30408C>T		intron_variant			XP_011531035.1
FSHR	XM_011532740.1	c.152+30408C>T		intron_variant			XP_011531042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.152+30408C>T		intron_variant		1	NM_000145.4	ENSP00000384708	P1
	ENST00000634588.1	n.492+177453G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37602 AN: 151792 Hom.: 4996 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.176

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.248 AC: 37651 AN: 151910 Hom.: 5007 Cov.: 32 AF XY: 0.253 AC XY: 18793 AN XY: 74242

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.249

Alfa AF: 0.231 Hom.: 1954

Bravo AF: 0.257

Asia WGS AF: 0.407 AC: 1412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.37

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: rs11125215; hg19: chr2-49350997; COSMIC: COSV58627297;