Variant 2-46297273-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000449347.5(EPAS1):c.-170-469G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 149,064 control chromosomes in the GnomAD database, including 1,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.073 ( 1197 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EPAS1
ENST00000449347.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.274

Variant links:

Genes affected

EPAS1 (HGNC:3374): (endothelial PAS domain protein 1) This gene encodes a transcription factor involved in the induction of genes regulated by oxygen, which is induced as oxygen levels fall. The encoded protein contains a basic-helix-loop-helix domain protein dimerization domain as well as a domain found in proteins in signal transduction pathways which respond to oxygen levels. Mutations in this gene are associated with erythrocytosis familial type 4. [provided by RefSeq, Nov 2009]

EPAS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 2-46297273-G-A is Benign according to our data. Variant chr2-46297273-G-A is described in ClinVar as [Benign]. Clinvar id is 1232911.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPAS1	ENST00000449347.5 link	c.-170-469G>A		intron_variant		3		ENSP00000406137.1		C9J9N2
EPAS1	ENST00000460015.1 link	n.432+3175G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0731

AC:

10882

AN:

148958

Hom.:

1189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0336

Gnomad ASJ

AF:

0.00117

Gnomad EAS

AF:

0.0101

Gnomad SAS

AF:

0.0551

Gnomad FIN

AF:

0.000947

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00307

Gnomad OTH

AF:

0.0555

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

AC XY:

AN XY:

Gnomad4 NFE exome

AF:

0.00

GnomAD4 genome

AF:

0.0732

AC:

10916

AN:

149064

Hom.:

1197

Cov.:

AF XY:

0.0722

AC XY:

5253

AN XY:

72714

show subpopulations

Gnomad4 AFR

AF:

0.237

Gnomad4 AMR

AF:

0.0336

Gnomad4 ASJ

AF:

0.00117

Gnomad4 EAS

AF:

0.00997

Gnomad4 SAS

AF:

0.0549

Gnomad4 FIN

AF:

0.000947

Gnomad4 NFE

AF:

0.00307

Gnomad4 OTH

AF:

0.0549

Alfa

AF:

0.00291

Hom.:

Bravo

AF:

0.0812

Asia WGS

AF:

0.0550

AC:

184

AN:

3358

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.97

Splicing

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