2-49114197-G-T

Variant names:

• chr2-49114197-G-T
• rs4971637
• NM_000145.4:c.152+40069C>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+40069C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 151,980 control chromosomes in the GnomAD database, including 2,531 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 0.17 (2531 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• 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

ENSG00000282890 (HGNC:58158):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 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+40069C>A		intron	N/A	NP_000136.2
	FSHR	NM_181446.3		c.152+40069C>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+40069C>A		intron	N/A	ENSP00000384708.2
	FSHR	ENST00000304421.8	TSL:1	c.152+40069C>A		intron	N/A	ENSP00000306780.4
	FSHR	ENST00000454032.5	TSL:1	c.152+40069C>A		intron	N/A	ENSP00000415504.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25592 AN: 151862 Hom.: 2530 Cov.: 32

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.168 AC: 25598 AN: 151980 Hom.: 2531 Cov.: 32 AF XY: 0.170 AC XY: 12656 AN XY: 74240

African (AFR) AF: 0.0793 AC: 3289 AN: 41488

American (AMR) AF: 0.207 AC: 3161 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 570 AN: 3472

East Asian (EAS) AF: 0.245 AC: 1258 AN: 5138

South Asian (SAS) AF: 0.267 AC: 1284 AN: 4816

European-Finnish (FIN) AF: 0.145 AC: 1532 AN: 10552

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13899 AN: 67948

Other (OTH) AF: 0.169 AC: 357 AN: 2108

Alfa AF: 0.0832 Hom.: 136

Bravo AF: 0.167

Asia WGS AF: 0.256 AC: 891 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.50
PhyloP100		0.070
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: rs4971637; hg19: chr2-49341336;