rs1007541

Variant names:

• chr2-48981895-C-T
• rs1007541
• NM_000145.4:c.668+1017G>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.668+1017G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,100 control chromosomes in the GnomAD database, including 2,135 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 0.16 (2135 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.668+1017G>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.668+1017G>A		intron_variant	Intron 8 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23920 AN: 151982 Hom.: 2129 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.158 AC: 23958 AN: 152100 Hom.: 2135 Cov.: 32 AF XY: 0.159 AC XY: 11836 AN XY: 74362

African (AFR) AF: 0.203 AC: 8431 AN: 41488

American (AMR) AF: 0.196 AC: 3002 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3472

East Asian (EAS) AF: 0.288 AC: 1486 AN: 5154

South Asian (SAS) AF: 0.0972 AC: 469 AN: 4826

European-Finnish (FIN) AF: 0.177 AC: 1874 AN: 10576

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7769 AN: 67992

Other (OTH) AF: 0.157 AC: 332 AN: 2108

Alfa AF: 0.134 Hom.: 1960

Bravo AF: 0.167

Asia WGS AF: 0.180 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.9
DANN	Benign	0.28
PhyloP100		0.049
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: rs1007541; hg19: chr2-49209034;