chr2-49013003-C-T

Variant names:

• chr2-49013003-C-T
• rs1316521
• NM_000145.4:c.374+4486G>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.374+4486G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,798 control chromosomes in the GnomAD database, including 33,277 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 0.63 (33277 hom., cov: 30)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000145.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHR	NM_000145.4	MANE Select	c.374+4486G>A		intron	N/A	NP_000136.2
	FSHR	NM_181446.3		c.374+4486G>A		intron	N/A	NP_852111.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHR	ENST00000406846.7	TSL:1 MANE Select	c.374+4486G>A		intron	N/A	ENSP00000384708.2
	FSHR	ENST00000304421.8	TSL:1	c.374+4486G>A		intron	N/A	ENSP00000306780.4
	FSHR	ENST00000454032.5	TSL:1	c.374+4486G>A		intron	N/A	ENSP00000415504.1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96230 AN: 151680 Hom.: 33285 Cov.: 30

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.634 AC: 96245 AN: 151798 Hom.: 33277 Cov.: 30 AF XY: 0.636 AC XY: 47210 AN XY: 74186

African (AFR) AF: 0.333 AC: 13775 AN: 41338

American (AMR) AF: 0.758 AC: 11554 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2371 AN: 3468

East Asian (EAS) AF: 0.769 AC: 3954 AN: 5140

South Asian (SAS) AF: 0.600 AC: 2888 AN: 4810

European-Finnish (FIN) AF: 0.763 AC: 8060 AN: 10566

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51450 AN: 67924

Other (OTH) AF: 0.654 AC: 1379 AN: 2110

Alfa AF: 0.588 Hom.: 2000

Bravo AF: 0.624

Asia WGS AF: 0.665 AC: 2310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.76
DANN	Benign	0.28
PhyloP100		-0.68
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: rs1316521; hg19: chr2-49240142;