2-49033403-G-C

Position:

• chr2-49033403-G-C

Variant summary

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

The NM_000145.4(FSHR):​c.225-13243C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,990 control chromosomes in the GnomAD database, including 14,182 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 0.42 (14182 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSHR	NM_000145.4	c.225-13243C>G		intron_variant		ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.225-13243C>G		intron_variant			NP_852111.2
FSHR	XM_011532733.3	c.225-13243C>G		intron_variant			XP_011531035.1
FSHR	XM_011532740.1	c.225-13243C>G		intron_variant			XP_011531042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.225-13243C>G		intron_variant		1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64227 AN: 151874 Hom.: 14156 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.423 AC: 64296 AN: 151990 Hom.: 14182 Cov.: 32 AF XY: 0.428 AC XY: 31825 AN XY: 74292

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.432

Alfa AF: 0.264 Hom.: 615

Bravo AF: 0.441

Asia WGS AF: 0.519 AC: 1804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.65

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: rs1290100; hg19: chr2-49260542;