rs6545094

Variant names:

• chr2-49039175-G-A
• rs6545094
• NM_000145.4:c.225-19015C>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.225-19015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,992 control chromosomes in the GnomAD database, including 12,687 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 0.41 (12687 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• 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

MIR548BAHG (HGNC:58158):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 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.225-19015C>T		intron	N/A	NP_000136.2
	FSHR	NM_181446.3		c.225-19015C>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.225-19015C>T		intron	N/A	ENSP00000384708.2	P23945-1
	FSHR	ENST00000304421.8	TSL:1	c.225-19015C>T		intron	N/A	ENSP00000306780.4	P23945-3
	FSHR	ENST00000454032.5	TSL:1	c.225-19015C>T		intron	N/A	ENSP00000415504.1	C9JDA1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61587 AN: 151874 Hom.: 12683 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.405 AC: 61622 AN: 151992 Hom.: 12687 Cov.: 32 AF XY: 0.405 AC XY: 30076 AN XY: 74294

African (AFR) AF: 0.366 AC: 15186 AN: 41470

American (AMR) AF: 0.414 AC: 6326 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1176 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2311 AN: 5156

South Asian (SAS) AF: 0.384 AC: 1852 AN: 4820

European-Finnish (FIN) AF: 0.461 AC: 4857 AN: 10532

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28534 AN: 67950

Other (OTH) AF: 0.394 AC: 830 AN: 2104

Alfa AF: 0.411 Hom.: 22580

Bravo AF: 0.403

Asia WGS AF: 0.427 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.21
PhyloP100		-0.20
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: rs6545094; hg19: chr2-49266314;