rs13396575

Variant names:

• chr2-48984774-G-C
• rs13396575
• NM_000145.4:c.525-1608C>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.525-1608C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,108 control chromosomes in the GnomAD database, including 1,198 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 0.11 (1198 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.525-1608C>G		intron_variant	Intron 6 of 9	ENST00000406846.7	NP_000136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.525-1608C>G		intron_variant	Intron 6 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17105 AN: 151990 Hom.: 1198 Cov.: 32

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.0967

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.112 AC: 17105 AN: 152108 Hom.: 1198 Cov.: 32 AF XY: 0.116 AC XY: 8647 AN XY: 74356

African (AFR) AF: 0.0539 AC: 2239 AN: 41510

American (AMR) AF: 0.161 AC: 2466 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 404 AN: 3464

East Asian (EAS) AF: 0.287 AC: 1482 AN: 5158

South Asian (SAS) AF: 0.0960 AC: 463 AN: 4824

European-Finnish (FIN) AF: 0.177 AC: 1874 AN: 10560

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7753 AN: 67980

Other (OTH) AF: 0.115 AC: 243 AN: 2112

Alfa AF: 0.115 Hom.: 134

Bravo AF: 0.113

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.71
PhyloP100		-0.22
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: rs13396575; hg19: chr2-49211913;