ENST00000634588.1:n.492+208151G>T

Variant names:

• chr2-49154556-G-T
• rs1298928775
• ENST00000634588.1:n.492+208151G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000634588.1(ENSG00000282890):​n.492+208151G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.000015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000049 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000282890 ENST00000634588.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 0 publications found

Genes affected

ENSG00000282890 (HGNC:58158):

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000634588.1. 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.-139C>A		upstream_gene	N/A	NP_000136.2
	FSHR	NM_181446.3		c.-139C>A		upstream_gene	N/A	NP_852111.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000282890	ENST00000634588.1	TSL:5	n.492+208151G>T		intron	N/A
	FSHR	ENST00000406846.7	TSL:1 MANE Select	c.-139C>A		upstream_gene	N/A	ENSP00000384708.2
	FSHR	ENST00000304421.8	TSL:1	c.-139C>A		upstream_gene	N/A	ENSP00000306780.4

Frequencies

GnomAD3 genomes AF: 0.0000151 AC: 2 AN: 132618 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000251

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000486 AC: 26 AN: 535304 Hom.: 0 Cov.: 8 AF XY: 0.0000601 AC XY: 17 AN XY: 282826

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000156 AC: 2 AN: 12838

American (AMR) AF: 0.0000496 AC: 1 AN: 20180

Ashkenazi Jewish (ASJ) AF: 0.0000685 AC: 1 AN: 14598

East Asian (EAS) AF: 0.00 AC: 0 AN: 28854

South Asian (SAS) AF: 0.0000822 AC: 4 AN: 48650

European-Finnish (FIN) AF: 0.0000693 AC: 2 AN: 28872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2060

European-Non Finnish (NFE) AF: 0.0000398 AC: 14 AN: 351726

Other (OTH) AF: 0.0000727 AC: 2 AN: 27526

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000151 AC: 2 AN: 132604 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 63960

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 35458

American (AMR) AF: 0.00 AC: 0 AN: 12510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3268

East Asian (EAS) AF: 0.00 AC: 0 AN: 4012

South Asian (SAS) AF: 0.00 AC: 0 AN: 3910

European-Finnish (FIN) AF: 0.000251 AC: 2 AN: 7954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62568

Other (OTH) AF: 0.00 AC: 0 AN: 1834

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.66
DANN	Benign	0.41
PhyloP100		0.074
PromoterAI		0.052	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1298928775; hg19: chr2-49381695;