rs971831

Variant names:

• chr2-49105231-G-A
• rs971831
• NM_000145.4:c.153-36941C>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.153-36941C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,910 control chromosomes in the GnomAD database, including 10,820 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 0.37 (10820 hom., cov: 31)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.153-36941C>T		intron_variant	Intron 1 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.153-36941C>T		intron_variant	Intron 1 of 8		NP_852111.2
FSHR	XM_011532733.3	c.153-36941C>T		intron_variant	Intron 1 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.153-36941C>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.153-36941C>T		intron_variant	Intron 1 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55988 AN: 151790 Hom.: 10802 Cov.: 31

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.369 AC: 56048 AN: 151910 Hom.: 10820 Cov.: 31 AF XY: 0.372 AC XY: 27605 AN XY: 74234

African (AFR) AF: 0.443 AC: 18332 AN: 41390

American (AMR) AF: 0.417 AC: 6363 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3470

East Asian (EAS) AF: 0.525 AC: 2692 AN: 5124

South Asian (SAS) AF: 0.344 AC: 1659 AN: 4816

European-Finnish (FIN) AF: 0.340 AC: 3587 AN: 10552

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21199 AN: 67964

Other (OTH) AF: 0.369 AC: 781 AN: 2116

Alfa AF: 0.332 Hom.: 26313

Bravo AF: 0.382

Asia WGS AF: 0.449 AC: 1561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.75
PhyloP100		-0.24
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: rs971831; hg19: chr2-49332370;