rs2268360

Variant names:

• chr2-48977494-C-A
• rs2268360
• NM_000145.4:c.668+5418G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-48977494-C-A
• chr2-48977494-C-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• ovarian hyperstimulation syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• ovarian dysgenesis 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• 46 XX gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000282890 (HGNC:58158):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.668+5418G>T		intron_variant	Intron 8 of 9	ENST00000406846.7	NP_000136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.668+5418G>T		intron_variant	Intron 8 of 9	1	NM_000145.4	ENSP00000384708.2

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

African (AFR) AF: 0.916 AC: 38019 AN: 41518

American (AMR) AF: 0.759 AC: 11584 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2657 AN: 3468

East Asian (EAS) AF: 0.725 AC: 3740 AN: 5160

South Asian (SAS) AF: 0.684 AC: 3297 AN: 4820

European-Finnish (FIN) AF: 0.764 AC: 8082 AN: 10572

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53333 AN: 67980

Other (OTH) AF: 0.797 AC: 1685 AN: 2114

Alfa AF: 0.796 Hom.: 10119

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
PhyloP100		0.064
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2268360; hg19: chr2-49204633;