2-49023832-A-G

Variant names:

• chr2-49023832-A-G
• rs12713034
• NM_000145.4:c.225-3672T>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.225-3672T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,050 control chromosomes in the GnomAD database, including 10,882 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 0.37 (10882 hom., cov: 31)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411
• Publications: 2 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 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.225-3672T>C		intron	N/A	NP_000136.2
	FSHR	NM_181446.3		c.225-3672T>C		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.225-3672T>C		intron	N/A	ENSP00000384708.2
	FSHR	ENST00000304421.8	TSL:1	c.225-3672T>C		intron	N/A	ENSP00000306780.4
	FSHR	ENST00000454032.5	TSL:1	c.225-3672T>C		intron	N/A	ENSP00000415504.1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55516 AN: 151932 Hom.: 10881 Cov.: 31

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.365 AC: 55532 AN: 152050 Hom.: 10882 Cov.: 31 AF XY: 0.363 AC XY: 26966 AN XY: 74332

African (AFR) AF: 0.243 AC: 10065 AN: 41500

American (AMR) AF: 0.306 AC: 4675 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1336 AN: 3472

East Asian (EAS) AF: 0.300 AC: 1551 AN: 5166

South Asian (SAS) AF: 0.362 AC: 1744 AN: 4818

European-Finnish (FIN) AF: 0.416 AC: 4384 AN: 10544

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30464 AN: 67940

Other (OTH) AF: 0.348 AC: 735 AN: 2114

Alfa AF: 0.415 Hom.: 48638

Bravo AF: 0.349

Asia WGS AF: 0.309 AC: 1076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.6
DANN	Benign	0.89
PhyloP100		0.41
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: rs12713034; hg19: chr2-49250971;