chr2-48974473-C-T

Position:

• chr2-48974473-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.669-5590G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,066 control chromosomes in the GnomAD database, including 23,651 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 0.54 (23651 hom., cov: 33)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

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]

FSHR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSHR	NM_000145.4	c.669-5590G>A		intron_variant		ENST00000406846.7	NP_000136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.669-5590G>A		intron_variant		1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81704 AN: 151948 Hom.: 23655 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.537 AC: 81715 AN: 152066 Hom.: 23651 Cov.: 33 AF XY: 0.539 AC XY: 40034 AN XY: 74328

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.554

Alfa AF: 0.616 Hom.: 29347

Bravo AF: 0.522

Asia WGS AF: 0.528 AC: 1837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.2
DANN	Benign	0.46

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: rs2268361; hg19: chr2-49201612;