2-49146463-A-G

Variant names:

• chr2-49146463-A-G
• rs4971665
• NM_000145.4:c.152+7803T>C

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+7803T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,828 control chromosomes in the GnomAD database, including 6,609 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 0.29 (6609 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392
• Publications: 0 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.152+7803T>C		intron_variant	Intron 1 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.152+7803T>C		intron_variant	Intron 1 of 8		NP_852111.2
FSHR	XM_011532733.3	c.152+7803T>C		intron_variant	Intron 1 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.152+7803T>C		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+7803T>C		intron_variant	Intron 1 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43691 AN: 151710 Hom.: 6596 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.288 AC: 43742 AN: 151828 Hom.: 6609 Cov.: 32 AF XY: 0.290 AC XY: 21526 AN XY: 74200

African (AFR) AF: 0.254 AC: 10536 AN: 41408

American (AMR) AF: 0.372 AC: 5669 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3472

East Asian (EAS) AF: 0.476 AC: 2435 AN: 5118

South Asian (SAS) AF: 0.356 AC: 1715 AN: 4818

European-Finnish (FIN) AF: 0.272 AC: 2873 AN: 10570

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18801 AN: 67904

Other (OTH) AF: 0.290 AC: 611 AN: 2108

Alfa AF: 0.150 Hom.: 293

Bravo AF: 0.297

Asia WGS AF: 0.429 AC: 1489 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.82
PhyloP100		0.39
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: rs4971665; hg19: chr2-49373602;