chr2-49039455-T-C

Variant names:

• chr2-49039455-T-C
• rs1277460
• NM_000145.4:c.225-19295A>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.225-19295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,262 control chromosomes in the GnomAD database, including 55,625 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 0.85 (55625 hom., cov: 33)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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]

ENSG00000282890 (HGNC:58158):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.225-19295A>G		intron_variant	Intron 2 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.225-19295A>G		intron_variant	Intron 2 of 8		NP_852111.2
FSHR	XM_011532733.3	c.225-19295A>G		intron_variant	Intron 2 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.225-19295A>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.225-19295A>G		intron_variant	Intron 2 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129569 AN: 152144 Hom.: 55559 Cov.: 33

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.928

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.839

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

GnomAD4 genome AF: 0.852 AC: 129691 AN: 152262 Hom.: 55625 Cov.: 33 AF XY: 0.852 AC XY: 63417 AN XY: 74450

African (AFR) AF: 0.943 AC: 39206 AN: 41556

American (AMR) AF: 0.861 AC: 13161 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2774 AN: 3470

East Asian (EAS) AF: 0.929 AC: 4808 AN: 5178

South Asian (SAS) AF: 0.751 AC: 3626 AN: 4828

European-Finnish (FIN) AF: 0.850 AC: 9010 AN: 10596

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54339 AN: 68022

Other (OTH) AF: 0.840 AC: 1777 AN: 2116

Alfa AF: 0.807 Hom.: 57642

Bravo AF: 0.860

Asia WGS AF: 0.844 AC: 2935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.30
DANN	Benign	0.35
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

Publications

LitVar

Other links and lift over

dbSNP: rs1277460; hg19: chr2-49266594;