chr2-49117675-G-A

Variant names:

• chr2-49117675-G-A
• rs2055571
• NM_000145.4:c.152+36591C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000145.4(FSHR):​c.152+36591C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 152,040 control chromosomes in the GnomAD database, including 18,057 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 0.47 (18057 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 2 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 (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.152+36591C>T		intron_variant	Intron 1 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.152+36591C>T		intron_variant	Intron 1 of 8		NP_852111.2
FSHR	XM_011532733.3	c.152+36591C>T		intron_variant	Intron 1 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.152+36591C>T		intron_variant	Intron 1 of 10		XP_011531042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.152+36591C>T		intron_variant	Intron 1 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72065 AN: 151924 Hom.: 18008 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.475 AC: 72168 AN: 152040 Hom.: 18057 Cov.: 32 AF XY: 0.478 AC XY: 35473 AN XY: 74276

African (AFR) AF: 0.603 AC: 25021 AN: 41482

American (AMR) AF: 0.539 AC: 8245 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1392 AN: 3466

East Asian (EAS) AF: 0.704 AC: 3629 AN: 5154

South Asian (SAS) AF: 0.491 AC: 2358 AN: 4806

European-Finnish (FIN) AF: 0.388 AC: 4091 AN: 10556

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25958 AN: 67968

Other (OTH) AF: 0.486 AC: 1028 AN: 2114

Alfa AF: 0.428 Hom.: 1938

Bravo AF: 0.496

Asia WGS AF: 0.621 AC: 2160 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	2.5
DANN	Benign	0.38
PhyloP100		0.33
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: rs2055571; hg19: chr2-49344814;