2-49143219-C-T

Variant names:

• chr2-49143219-C-T
• rs1157876
• NM_000145.4:c.152+11047G>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.152+11047G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,864 control chromosomes in the GnomAD database, including 6,136 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 0.28 (6136 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 5 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 = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.152+11047G>A		intron_variant	Intron 1 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.152+11047G>A		intron_variant	Intron 1 of 8		NP_852111.2
FSHR	XM_011532733.3	c.152+11047G>A		intron_variant	Intron 1 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.152+11047G>A		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+11047G>A		intron_variant	Intron 1 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42036 AN: 151746 Hom.: 6122 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.277 AC: 42088 AN: 151864 Hom.: 6136 Cov.: 32 AF XY: 0.279 AC XY: 20733 AN XY: 74208

African (AFR) AF: 0.251 AC: 10390 AN: 41428

American (AMR) AF: 0.363 AC: 5539 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3468

East Asian (EAS) AF: 0.472 AC: 2422 AN: 5128

South Asian (SAS) AF: 0.338 AC: 1621 AN: 4796

European-Finnish (FIN) AF: 0.256 AC: 2700 AN: 10540

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.262 AC: 17787 AN: 67946

Other (OTH) AF: 0.277 AC: 584 AN: 2110

Alfa AF: 0.206 Hom.: 673

Bravo AF: 0.287

Asia WGS AF: 0.419 AC: 1456 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	0.095
DANN	Benign	0.38
PhyloP100		-2.0
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: rs1157876; hg19: chr2-49370358;