2-48977971-G-A

Variant names:

• chr2-48977971-G-A
• rs2268359
• NM_000145.4:c.668+4941C>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.668+4941C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,066 control chromosomes in the GnomAD database, including 1,900 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 0.15 (1900 hom., cov: 33)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.964
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.668+4941C>T		intron_variant	Intron 8 of 9	ENST00000406846.7	NP_000136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.668+4941C>T		intron_variant	Intron 8 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22413 AN: 151946 Hom.: 1894 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.0992

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.0966

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.148 AC: 22450 AN: 152066 Hom.: 1900 Cov.: 33 AF XY: 0.150 AC XY: 11112 AN XY: 74306

African (AFR) AF: 0.190 AC: 7874 AN: 41472

American (AMR) AF: 0.176 AC: 2692 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0992 AC: 344 AN: 3466

East Asian (EAS) AF: 0.297 AC: 1538 AN: 5174

South Asian (SAS) AF: 0.0963 AC: 464 AN: 4820

European-Finnish (FIN) AF: 0.172 AC: 1817 AN: 10548

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7226 AN: 68002

Other (OTH) AF: 0.143 AC: 302 AN: 2112

Alfa AF: 0.124 Hom.: 2813

Bravo AF: 0.154

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.51
PhyloP100		0.96
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: rs2268359; hg19: chr2-49205110;