2-49060921-G-T

Variant names:

• chr2-49060921-G-T
• rs11680730
• NM_000145.4:c.224+7298C>A

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+7298C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,898 control chromosomes in the GnomAD database, including 9,713 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 0.35 (9713 hom., cov: 31)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000145.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHR	NM_000145.4	MANE Select	c.224+7298C>A		intron	N/A	NP_000136.2
	FSHR	NM_181446.3		c.224+7298C>A		intron	N/A	NP_852111.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHR	ENST00000406846.7	TSL:1 MANE Select	c.224+7298C>A		intron	N/A	ENSP00000384708.2
	FSHR	ENST00000304421.8	TSL:1	c.224+7298C>A		intron	N/A	ENSP00000306780.4
	FSHR	ENST00000454032.5	TSL:1	c.224+7298C>A		intron	N/A	ENSP00000415504.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52522 AN: 151780 Hom.: 9706 Cov.: 31

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.346 AC: 52556 AN: 151898 Hom.: 9713 Cov.: 31 AF XY: 0.347 AC XY: 25752 AN XY: 74212

African (AFR) AF: 0.213 AC: 8809 AN: 41416

American (AMR) AF: 0.409 AC: 6242 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1190 AN: 3470

East Asian (EAS) AF: 0.490 AC: 2511 AN: 5126

South Asian (SAS) AF: 0.470 AC: 2262 AN: 4808

European-Finnish (FIN) AF: 0.315 AC: 3328 AN: 10550

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.396 AC: 26933 AN: 67940

Other (OTH) AF: 0.375 AC: 792 AN: 2114

Alfa AF: 0.352 Hom.: 1646

Bravo AF: 0.346

Asia WGS AF: 0.459 AC: 1596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.44
PhyloP100		0.15
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: rs11680730; hg19: chr2-49288060;