NM_000145.4:c.224+19116T>C

Variant names:

• chr2-49049103-A-G
• rs3913665
• NM_000145.4:c.224+19116T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000145.4(FSHR):​c.224+19116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,602 control chromosomes in the GnomAD database, including 24,217 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 0.56 (24217 hom., cov: 30)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 3 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.224+19116T>C		intron_variant	Intron 2 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.224+19116T>C		intron_variant	Intron 2 of 8		NP_852111.2
FSHR	XM_011532733.3	c.224+19116T>C		intron_variant	Intron 2 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.224+19116T>C		intron_variant	Intron 2 of 10		XP_011531042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.224+19116T>C		intron_variant	Intron 2 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84193 AN: 151484 Hom.: 24194 Cov.: 30

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.556 AC: 84262 AN: 151602 Hom.: 24217 Cov.: 30 AF XY: 0.558 AC XY: 41290 AN XY: 74036

African (AFR) AF: 0.403 AC: 16657 AN: 41326

American (AMR) AF: 0.641 AC: 9753 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2034 AN: 3466

East Asian (EAS) AF: 0.752 AC: 3870 AN: 5144

South Asian (SAS) AF: 0.588 AC: 2828 AN: 4806

European-Finnish (FIN) AF: 0.623 AC: 6510 AN: 10442

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40572 AN: 67890

Other (OTH) AF: 0.598 AC: 1261 AN: 2110

Alfa AF: 0.587 Hom.: 43795

Bravo AF: 0.555

Asia WGS AF: 0.664 AC: 2308 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.59
PhyloP100		1.8
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: rs3913665; hg19: chr2-49276242;