rs12713027

Variant names:

• chr2-48972309-A-G
• rs12713027
• NM_000145.4:c.669-3426T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-48972309-A-G
• chr2-48972309-A-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.669-3426T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,016 control chromosomes in the GnomAD database, including 6,574 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 0.29 (6574 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• 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 (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000145.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHR	NM_000145.4	MANE Select	c.669-3426T>C		intron	N/A	NP_000136.2
	FSHR	NM_181446.3		c.591-3426T>C		intron	N/A	NP_852111.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHR	ENST00000406846.7	TSL:1 MANE Select	c.669-3426T>C		intron	N/A	ENSP00000384708.2
	FSHR	ENST00000304421.8	TSL:1	c.591-3426T>C		intron	N/A	ENSP00000306780.4
	FSHR	ENST00000454032.5	TSL:1	c.669-8343T>C		intron	N/A	ENSP00000415504.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43690 AN: 151898 Hom.: 6566 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.288 AC: 43744 AN: 152016 Hom.: 6574 Cov.: 32 AF XY: 0.289 AC XY: 21465 AN XY: 74304

African (AFR) AF: 0.370 AC: 15334 AN: 41450

American (AMR) AF: 0.240 AC: 3674 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1019 AN: 3466

East Asian (EAS) AF: 0.270 AC: 1396 AN: 5166

South Asian (SAS) AF: 0.205 AC: 984 AN: 4810

European-Finnish (FIN) AF: 0.303 AC: 3198 AN: 10562

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17268 AN: 67972

Other (OTH) AF: 0.274 AC: 578 AN: 2108

Alfa AF: 0.260 Hom.: 16769

Bravo AF: 0.287

Asia WGS AF: 0.256 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.072
DANN	Benign	0.65
PhyloP100		-0.38
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: rs12713027; hg19: chr2-49199448;