rs12473870

Variant names:

• chr2-49065202-G-A
• rs12473870
• NM_000145.4:c.224+3017C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-49065202-G-A
• chr2-49065202-G-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+3017C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,958 control chromosomes in the GnomAD database, including 12,672 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 0.41 (12672 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.224+3017C>T		intron_variant	Intron 2 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.224+3017C>T		intron_variant	Intron 2 of 8		NP_852111.2
FSHR	XM_011532733.3	c.224+3017C>T		intron_variant	Intron 2 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.224+3017C>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.224+3017C>T		intron_variant	Intron 2 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61628 AN: 151838 Hom.: 12660 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.406 AC: 61684 AN: 151958 Hom.: 12672 Cov.: 32 AF XY: 0.406 AC XY: 30185 AN XY: 74258

African (AFR) AF: 0.408 AC: 16909 AN: 41460

American (AMR) AF: 0.430 AC: 6541 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1272 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2773 AN: 5156

South Asian (SAS) AF: 0.480 AC: 2310 AN: 4814

European-Finnish (FIN) AF: 0.317 AC: 3350 AN: 10566

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27154 AN: 67958

Other (OTH) AF: 0.418 AC: 882 AN: 2108

Alfa AF: 0.398 Hom.: 2001

Bravo AF: 0.413

Asia WGS AF: 0.496 AC: 1726 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	5.0
DANN	Benign	0.69
PhyloP100		-0.056
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: rs12473870; hg19: chr2-49292341;