Variant 2-46356142-C-CT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001430.5(EPAS1):c.218-9_218-8insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,191,614 control chromosomes in the GnomAD database, including 7,274 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2444 hom., cov: 23)

Exomes 𝑓: 0.15 ( 7274 hom. )

Failed GnomAD Quality Control

Consequence

EPAS1
NM_001430.5 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.628

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 -16 ACMG points.

BP6

Variant 2-46356142-C-CT is Benign according to our data. Variant chr2-46356142-C-CT is described in ClinVar as [Benign]. Clinvar id is 336245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPAS1	NM_001430.5 linkuse as main transcript	c.218-9_218-8insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000263734.5	NP_001421.2
EPAS1	XM_011532698.3 linkuse as main transcript	c.257-9_257-8insT		splice_polypyrimidine_tract_variant, intron_variant			XP_011531000.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
EPAS1	ENST00000263734.5 linkuse as main transcript	c.218-9_218-8insT	splice_polypyrimidine_tract_variant, intron_variant		1	NM_001430.5	ENSP00000263734	P1
EPAS1	ENST00000449347.5 linkuse as main transcript	c.218-9_218-8insT	splice_polypyrimidine_tract_variant, intron_variant		3		ENSP00000406137
EPAS1	ENST00000463191.1 linkuse as main transcript	n.28_29insT	non_coding_transcript_exon_variant	1/4	2
EPAS1	ENST00000475822.1 linkuse as main transcript	n.409-9_409-8insT	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

26281

AN:

143690

Hom.:

2435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.0940

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.137

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.175

GnomAD4 exome

AF:

0.148

AC:

176441

AN:

1191614

Hom.:

7274

Cov.:

AF XY:

0.151

AC XY:

90343

AN XY:

598802

show subpopulations

Gnomad4 AFR exome

AF:

0.199

Gnomad4 AMR exome

AF:

0.296

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.0814

Gnomad4 SAS exome

AF:

0.253

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.131

Gnomad4 OTH exome

AF:

0.146

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.183

AC:

26319

AN:

143808

Hom.:

2444

Cov.:

AF XY:

0.185

AC XY:

12877

AN XY:

69572

show subpopulations

Gnomad4 AFR

AF:

0.232

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.208

Gnomad4 EAS

AF:

0.0942

Gnomad4 SAS

AF:

0.280

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.173

Alfa

AF:

0.154

Hom.:

165

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial erythrocytosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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