rs17038141

Variant names:

• chr2-49045631-G-A
• rs17038141
• NM_000145.4:c.224+22588C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000145.4(FSHR):​c.224+22588C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,136 control chromosomes in the GnomAD database, including 1,416 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 0.13 (1416 hom., cov: 33)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.796
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 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.224+22588C>T		intron	N/A	NP_000136.2
	FSHR	NM_181446.3		c.224+22588C>T		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.224+22588C>T		intron	N/A	ENSP00000384708.2
	FSHR	ENST00000304421.8	TSL:1	c.224+22588C>T		intron	N/A	ENSP00000306780.4
	FSHR	ENST00000454032.5	TSL:1	c.224+22588C>T		intron	N/A	ENSP00000415504.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20519 AN: 152018 Hom.: 1416 Cov.: 33

Gnomad AFR AF: 0.0958

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.135 AC: 20538 AN: 152136 Hom.: 1416 Cov.: 33 AF XY: 0.136 AC XY: 10086 AN XY: 74346

African (AFR) AF: 0.0959 AC: 3981 AN: 41522

American (AMR) AF: 0.168 AC: 2569 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 608 AN: 3472

East Asian (EAS) AF: 0.214 AC: 1106 AN: 5170

South Asian (SAS) AF: 0.180 AC: 867 AN: 4818

European-Finnish (FIN) AF: 0.124 AC: 1312 AN: 10576

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9593 AN: 68000

Other (OTH) AF: 0.164 AC: 346 AN: 2110

Alfa AF: 0.138 Hom.: 812

Bravo AF: 0.138

Asia WGS AF: 0.186 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.5
DANN	Benign	0.74
PhyloP100		0.80
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: rs17038141; hg19: chr2-49272770; COSMIC: COSV58633979;