rs2268360

chr2-48977494-C-Achr2-48977494-C-G

Variant summary

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

The NM_000145.4(FSHR):c.668+5418G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,108 control chromosomes in the GnomAD database, including 50,303 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 0.81 (50303 hom., cov: 31)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSHR	NM_000145.4	c.668+5418G>T		intron_variant		ENST00000406846.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSHR	ENST00000406846.7	c.668+5418G>T		intron_variant		1	NM_000145.4	P1
	ENST00000634588.1	n.492+31089C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123092 AN: 151990 Hom.: 50254 Cov.: 31

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.794

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

GnomAD4 genome AF: 0.810 AC: 123198 AN: 152108 Hom.: 50303 Cov.: 31 AF XY: 0.806 AC XY: 59897 AN XY: 74350

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.725

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.797

Alfa AF: 0.794 Hom.: 9819

Bravo AF: 0.812

Asia WGS AF: 0.732 AC: 2546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.0
Dann	Benign	0.43

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: rs2268360; hg19: chr2-49204633;