chr2-49038693-C-A

Variant names:

• chr2-49038693-C-A
• rs6741370
• NM_000145.4:c.225-18533G>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.225-18533G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 147,016 control chromosomes in the GnomAD database, including 4,292 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 0.23 (4292 hom., cov: 28)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.225-18533G>T		intron_variant	Intron 2 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.225-18533G>T		intron_variant	Intron 2 of 8		NP_852111.2
FSHR	XM_011532733.3	c.225-18533G>T		intron_variant	Intron 2 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.225-18533G>T		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.225-18533G>T		intron_variant	Intron 2 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.231 AC: 33947 AN: 146980 Hom.: 4293 Cov.: 28

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.231 AC: 33954 AN: 147016 Hom.: 4292 Cov.: 28 AF XY: 0.230 AC XY: 16482 AN XY: 71574

African (AFR) AF: 0.299 AC: 11950 AN: 39978

American (AMR) AF: 0.245 AC: 3612 AN: 14768

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 915 AN: 3430

East Asian (EAS) AF: 0.332 AC: 1673 AN: 5036

South Asian (SAS) AF: 0.197 AC: 914 AN: 4650

European-Finnish (FIN) AF: 0.163 AC: 1500 AN: 9184

Middle Eastern (MID) AF: 0.279 AC: 78 AN: 280

European-Non Finnish (NFE) AF: 0.190 AC: 12657 AN: 66776

Other (OTH) AF: 0.252 AC: 510 AN: 2020

Alfa AF: 0.206 Hom.: 923

Bravo AF: 0.242

Asia WGS AF: 0.244 AC: 841 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.67
DANN	Benign	0.33
PhyloP100		-0.59
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: rs6741370; hg19: chr2-49265832;