chr2-49065223-C-T

Variant names:

• chr2-49065223-C-T
• rs12473815
• NM_000145.4:c.224+2996G>A

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+2996G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,892 control chromosomes in the GnomAD database, including 9,701 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 0.35 (9701 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 6 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 = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.224+2996G>A		intron_variant	Intron 2 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.224+2996G>A		intron_variant	Intron 2 of 8		NP_852111.2
FSHR	XM_011532733.3	c.224+2996G>A		intron_variant	Intron 2 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.224+2996G>A		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+2996G>A		intron_variant	Intron 2 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52387 AN: 151774 Hom.: 9695 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.345 AC: 52417 AN: 151892 Hom.: 9701 Cov.: 32 AF XY: 0.346 AC XY: 25702 AN XY: 74220

African (AFR) AF: 0.207 AC: 8568 AN: 41424

American (AMR) AF: 0.409 AC: 6232 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1252 AN: 3468

East Asian (EAS) AF: 0.489 AC: 2531 AN: 5172

South Asian (SAS) AF: 0.472 AC: 2271 AN: 4812

European-Finnish (FIN) AF: 0.316 AC: 3335 AN: 10538

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26949 AN: 67942

Other (OTH) AF: 0.375 AC: 791 AN: 2110

Alfa AF: 0.276 Hom.: 1040

Bravo AF: 0.345

Asia WGS AF: 0.458 AC: 1592 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.38
DANN	Benign	0.45
PhyloP100		-1.9
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: rs12473815; hg19: chr2-49292362;