rs4971884

Variant names:

• chr2-49112209-G-A
• rs4971884
• NM_000145.4:c.152+42057C>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.152+42057C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,084 control chromosomes in the GnomAD database, including 4,269 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 0.22 (4269 hom., cov: 33)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.152+42057C>T		intron_variant	Intron 1 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.152+42057C>T		intron_variant	Intron 1 of 8		NP_852111.2
FSHR	XM_011532733.3	c.152+42057C>T		intron_variant	Intron 1 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.152+42057C>T		intron_variant	Intron 1 of 10		XP_011531042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.152+42057C>T		intron_variant	Intron 1 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32687 AN: 151966 Hom.: 4263 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.215 AC: 32706 AN: 152084 Hom.: 4269 Cov.: 33 AF XY: 0.221 AC XY: 16462 AN XY: 74348

African (AFR) AF: 0.104 AC: 4315 AN: 41496

American (AMR) AF: 0.331 AC: 5061 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 640 AN: 3470

East Asian (EAS) AF: 0.467 AC: 2403 AN: 5148

South Asian (SAS) AF: 0.307 AC: 1482 AN: 4822

European-Finnish (FIN) AF: 0.250 AC: 2644 AN: 10584

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15436 AN: 67974

Other (OTH) AF: 0.226 AC: 477 AN: 2112

Alfa AF: 0.215 Hom.: 522

Bravo AF: 0.220

Asia WGS AF: 0.394 AC: 1367 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.84
DANN	Benign	0.45
PhyloP100		-0.046
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: rs4971884; hg19: chr2-49339348;