rs11125215

Variant names:

• chr2-49123858-G-A
• rs11125215
• NM_000145.4:c.152+30408C>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.152+30408C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,910 control chromosomes in the GnomAD database, including 5,007 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 0.25 (5007 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417
• Publications: 0 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

MIR548BAHG (HGNC:58158):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHR	NM_000145.4	MANE Select	c.152+30408C>T		intron	N/A	NP_000136.2
	FSHR	NM_181446.3		c.152+30408C>T		intron	N/A	NP_852111.2	P23945-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHR	ENST00000406846.7	TSL:1 MANE Select	c.152+30408C>T		intron	N/A	ENSP00000384708.2	P23945-1
	FSHR	ENST00000304421.8	TSL:1	c.152+30408C>T		intron	N/A	ENSP00000306780.4	P23945-3
	FSHR	ENST00000454032.5	TSL:1	c.152+30408C>T		intron	N/A	ENSP00000415504.1	C9JDA1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37602 AN: 151792 Hom.: 4996 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.176

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.248 AC: 37651 AN: 151910 Hom.: 5007 Cov.: 32 AF XY: 0.253 AC XY: 18793 AN XY: 74242

African (AFR) AF: 0.230 AC: 9544 AN: 41410

American (AMR) AF: 0.332 AC: 5064 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 650 AN: 3468

East Asian (EAS) AF: 0.472 AC: 2425 AN: 5136

South Asian (SAS) AF: 0.308 AC: 1480 AN: 4806

European-Finnish (FIN) AF: 0.249 AC: 2624 AN: 10556

Middle Eastern (MID) AF: 0.186 AC: 54 AN: 290

European-Non Finnish (NFE) AF: 0.222 AC: 15090 AN: 67960

Other (OTH) AF: 0.249 AC: 525 AN: 2110

Alfa AF: 0.230 Hom.: 2142

Bravo AF: 0.257

Asia WGS AF: 0.407 AC: 1412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.37
PhyloP100		0.42
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: rs11125215; hg19: chr2-49350997; COSMIC: COSV58627297;