2-49065223-C-T

Position:

• chr2-49065223-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.224+2996G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,892 control chromosomes in the GnomAD database, including 9,701 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 0.35 (9701 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

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]

ENSG00000282890 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSHR	NM_000145.4	c.224+2996G>A		intron_variant		ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.224+2996G>A		intron_variant			NP_852111.2
FSHR	XM_011532733.3	c.224+2996G>A		intron_variant			XP_011531035.1
FSHR	XM_011532740.1	c.224+2996G>A		intron_variant			XP_011531042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.224+2996G>A		intron_variant		1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52387 AN: 151774 Hom.: 9695 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.345 AC: 52417 AN: 151892 Hom.: 9701 Cov.: 32 AF XY: 0.346 AC XY: 25702 AN XY: 74220

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.375

Alfa AF: 0.279 Hom.: 1016

Bravo AF: 0.345

Asia WGS AF: 0.458 AC: 1592 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.38
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: rs12473815; hg19: chr2-49292362;