chr2-48994007-T-C

Variant names:

• chr2-48994007-T-C
• rs4494802
• NM_000145.4:c.375-3370A>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.375-3370A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 152,256 control chromosomes in the GnomAD database, including 844 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 0.093 (844 hom., cov: 33)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.375-3370A>G		intron_variant	Intron 4 of 9	ENST00000406846.7	NP_000136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.375-3370A>G		intron_variant	Intron 4 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14138 AN: 152138 Hom.: 841 Cov.: 33

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0829

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0930 AC: 14159 AN: 152256 Hom.: 844 Cov.: 33 AF XY: 0.0950 AC XY: 7072 AN XY: 74430

African (AFR) AF: 0.0241 AC: 1002 AN: 41582

American (AMR) AF: 0.0833 AC: 1273 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3466

East Asian (EAS) AF: 0.170 AC: 879 AN: 5178

South Asian (SAS) AF: 0.121 AC: 586 AN: 4826

European-Finnish (FIN) AF: 0.137 AC: 1448 AN: 10598

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8132 AN: 68002

Other (OTH) AF: 0.108 AC: 229 AN: 2112

Alfa AF: 0.108 Hom.: 149

Bravo AF: 0.0867

Asia WGS AF: 0.141 AC: 491 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	0.11
DANN	Benign	0.71
PhyloP100		-1.1
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: rs4494802; hg19: chr2-49221146;