2-48974473-C-T

Variant names:

• chr2-48974473-C-T
• rs2268361
• NM_000145.4:c.669-5590G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 43 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=-0.88).
• 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 rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.669-5590G>A		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.669-5590G>A		intron_variant	Intron 8 of 9	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

African (AFR) AF: 0.304 AC: 12624 AN: 41476

American (AMR) AF: 0.614 AC: 9385 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2016 AN: 3466

East Asian (EAS) AF: 0.517 AC: 2670 AN: 5168

South Asian (SAS) AF: 0.543 AC: 2615 AN: 4818

European-Finnish (FIN) AF: 0.634 AC: 6711 AN: 10580

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43898 AN: 67958

Other (OTH) AF: 0.554 AC: 1168 AN: 2108

Alfa AF: 0.598 Hom.: 78155

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
PhyloP100		0.18
Mutation Taster		=99/1	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: rs2268361; hg19: chr2-49201612;