2-49138908-C-T

Variant names:

• chr2-49138908-C-T
• rs17038320
• NM_000145.4:c.152+15358G>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.152+15358G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,850 control chromosomes in the GnomAD database, including 1,639 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 0.14 (1639 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.152+15358G>A		intron_variant	Intron 1 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.152+15358G>A		intron_variant	Intron 1 of 8		NP_852111.2
FSHR	XM_011532733.3	c.152+15358G>A		intron_variant	Intron 1 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.152+15358G>A		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+15358G>A		intron_variant	Intron 1 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21925 AN: 151732 Hom.: 1639 Cov.: 32

Gnomad AFR AF: 0.0989

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.144 AC: 21939 AN: 151850 Hom.: 1639 Cov.: 32 AF XY: 0.145 AC XY: 10766 AN XY: 74194

African (AFR) AF: 0.0989 AC: 4099 AN: 41428

American (AMR) AF: 0.178 AC: 2708 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 699 AN: 3468

East Asian (EAS) AF: 0.228 AC: 1180 AN: 5168

South Asian (SAS) AF: 0.175 AC: 838 AN: 4802

European-Finnish (FIN) AF: 0.140 AC: 1475 AN: 10504

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10412 AN: 67928

Other (OTH) AF: 0.177 AC: 373 AN: 2106

Alfa AF: 0.150 Hom.: 2925

Bravo AF: 0.147

Asia WGS AF: 0.193 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.56
PhyloP100		-0.23
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: rs17038320; hg19: chr2-49366047;