2-49024121-C-T

Variant names:

• chr2-49024121-C-T
• rs17038059
• NM_000145.4:c.225-3961G>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.225-3961G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,994 control chromosomes in the GnomAD database, including 5,733 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 0.26 (5733 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.225-3961G>A		intron_variant	Intron 2 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.225-3961G>A		intron_variant	Intron 2 of 8		NP_852111.2
FSHR	XM_011532733.3	c.225-3961G>A		intron_variant	Intron 2 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.225-3961G>A		intron_variant	Intron 2 of 10		XP_011531042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.225-3961G>A		intron_variant	Intron 2 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38890 AN: 151876 Hom.: 5719 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.256 AC: 38940 AN: 151994 Hom.: 5733 Cov.: 32 AF XY: 0.259 AC XY: 19205 AN XY: 74280

African (AFR) AF: 0.339 AC: 14056 AN: 41426

American (AMR) AF: 0.361 AC: 5511 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 769 AN: 3468

East Asian (EAS) AF: 0.474 AC: 2450 AN: 5166

South Asian (SAS) AF: 0.236 AC: 1137 AN: 4818

European-Finnish (FIN) AF: 0.225 AC: 2370 AN: 10548

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.174 AC: 11850 AN: 67998

Other (OTH) AF: 0.292 AC: 616 AN: 2108

Alfa AF: 0.205 Hom.: 6202

Bravo AF: 0.277

Asia WGS AF: 0.378 AC: 1314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.092
DANN	Benign	0.62
PhyloP100		-0.86
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: rs17038059; hg19: chr2-49251260;