rs12713027

Positions:

• chr2-48972309-A-G
• chr2-48972309-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSHR	NM_000145.4	c.669-3426T>C		intron_variant		ENST00000406846.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSHR	ENST00000406846.7	c.669-3426T>C		intron_variant		1	NM_000145.4	P1
	ENST00000634588.1	n.492+25904A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.274

Alfa AF: 0.254 Hom.: 10143

Bravo AF: 0.287

Asia WGS AF: 0.256 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.072
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs12713027; hg19: chr2-49199448;