Variant 2-48962487-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000406846.7(FSHR):c.*246T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 487,370 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 55 hom., cov: 32)

Exomes 𝑓: 0.028 ( 193 hom. )

Consequence

FSHR
ENST00000406846.7 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.63

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-48962487-A-T is Benign according to our data. Variant chr2-48962487-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 336476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0213 (3244/152330) while in subpopulation SAS AF= 0.033 (159/4824). AF 95% confidence interval is 0.0309. There are 55 homozygotes in gnomad4. There are 1600 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 55 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSHR	NM_000145.4 linkuse as main transcript	c.*246T>A		3_prime_UTR_variant	10/10	ENST00000406846.7	NP_000136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7 linkuse as main transcript	c.*246T>A		3_prime_UTR_variant	10/10	1	NM_000145.4	ENSP00000384708	P1
	ENST00000634588.1 linkuse as main transcript	n.492+16082A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0213

AC:

3248

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00576

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0336

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0320

Gnomad OTH

AF:

0.0220

GnomAD4 exome

AF:

0.0282

AC:

9453

AN:

335040

Hom.:

193

Cov.:

AF XY:

0.0290

AC XY:

5177

AN XY:

178592

show subpopulations

Gnomad4 AFR exome

AF:

0.00565

Gnomad4 AMR exome

AF:

0.0148

Gnomad4 ASJ exome

AF:

0.0242

Gnomad4 EAS exome

AF:

0.000245

Gnomad4 SAS exome

AF:

0.0348

Gnomad4 FIN exome

AF:

0.0255

Gnomad4 NFE exome

AF:

0.0322

Gnomad4 OTH exome

AF:

0.0261

GnomAD4 genome

AF:

0.0213

AC:

3244

AN:

152330

Hom.:

Cov.:

AF XY:

0.0215

AC XY:

1600

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00575

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0330

Gnomad4 FIN

AF:

0.0228

Gnomad4 NFE

AF:

0.0320

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0254

Hom.:

Bravo

AF:

0.0192

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Ovarian dysgenesis 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Ovarian hyperstimulation syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

DANN

Benign

0.56

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over