2-49033403-G-C

Variant names:

• chr2-49033403-G-C
• rs1290100
• NM_000145.4:c.225-13243C>G

Variant summary

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

The NM_000145.4(FSHR):​c.225-13243C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,990 control chromosomes in the GnomAD database, including 14,182 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 0.42 (14182 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.225-13243C>G		intron_variant	Intron 2 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.225-13243C>G		intron_variant	Intron 2 of 8		NP_852111.2
FSHR	XM_011532733.3	c.225-13243C>G		intron_variant	Intron 2 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.225-13243C>G		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.225-13243C>G		intron_variant	Intron 2 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64227 AN: 151874 Hom.: 14156 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.423 AC: 64296 AN: 151990 Hom.: 14182 Cov.: 32 AF XY: 0.428 AC XY: 31825 AN XY: 74292

African (AFR) AF: 0.452 AC: 18722 AN: 41442

American (AMR) AF: 0.563 AC: 8606 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1376 AN: 3470

East Asian (EAS) AF: 0.663 AC: 3407 AN: 5142

South Asian (SAS) AF: 0.377 AC: 1817 AN: 4816

European-Finnish (FIN) AF: 0.439 AC: 4646 AN: 10572

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24367 AN: 67948

Other (OTH) AF: 0.432 AC: 913 AN: 2112

Alfa AF: 0.264 Hom.: 615

Bravo AF: 0.441

Asia WGS AF: 0.519 AC: 1804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.65
PhyloP100		0.013
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: rs1290100; hg19: chr2-49260542;