2-49145305-C-T

Variant names:

• chr2-49145305-C-T
• rs10495968
• NM_000145.4:c.152+8961G>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.152+8961G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,964 control chromosomes in the GnomAD database, including 6,528 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 0.29 (6528 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• 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

MIR548BAHG (HGNC:58158):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 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.152+8961G>A		intron	N/A	NP_000136.2
	FSHR	NM_181446.3		c.152+8961G>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.152+8961G>A		intron	N/A	ENSP00000384708.2
	FSHR	ENST00000304421.8	TSL:1	c.152+8961G>A		intron	N/A	ENSP00000306780.4
	FSHR	ENST00000454032.5	TSL:1	c.152+8961G>A		intron	N/A	ENSP00000415504.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43463 AN: 151846 Hom.: 6516 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.286 AC: 43513 AN: 151964 Hom.: 6528 Cov.: 32 AF XY: 0.288 AC XY: 21410 AN XY: 74270

African (AFR) AF: 0.253 AC: 10508 AN: 41458

American (AMR) AF: 0.370 AC: 5640 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3470

East Asian (EAS) AF: 0.473 AC: 2439 AN: 5156

South Asian (SAS) AF: 0.348 AC: 1678 AN: 4816

European-Finnish (FIN) AF: 0.273 AC: 2876 AN: 10554

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18687 AN: 67954

Other (OTH) AF: 0.284 AC: 596 AN: 2102

Alfa AF: 0.164 Hom.: 329

Bravo AF: 0.295

Asia WGS AF: 0.423 AC: 1467 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.20
PhyloP100		-0.44
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: rs10495968; hg19: chr2-49372444;