2-46356133-AC-A

Position:

• chr2-46356133-AC-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000263734.5(EPAS1):​c.218-8delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 25)
  • Exomes 𝑓: 0.058 (14 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPAS1 ENST00000263734.5 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0370

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 2-46356133-AC-A is Benign according to our data. Variant chr2-46356133-AC-A is described in ClinVar as [Benign]. Clinvar id is 1697878.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPAS1	NM_001430.5	c.218-8delC		splice_region_variant, intron_variant		ENST00000263734.5	NP_001421.2
EPAS1	XM_011532698.3	c.257-8delC		splice_region_variant, intron_variant			XP_011531000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPAS1	ENST00000263734.5	c.218-8delC		splice_region_variant, intron_variant		1	NM_001430.5	ENSP00000263734.3
EPAS1	ENST00000449347.5	c.218-8delC		splice_region_variant, intron_variant		3		ENSP00000406137.1
EPAS1	ENST00000463191.1	n.29delC		non_coding_transcript_exon_variant	1/4	2
EPAS1	ENST00000475822.1	n.409-8delC		splice_region_variant, intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 149 AN: 78796 Hom.: 1 Cov.: 25 FAILED QC

Gnomad AFR AF: 0.000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000629

Gnomad ASJ AF: 0.00509

Gnomad EAS AF: 0.0136

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.00344

Gnomad MID AF: 0.0205

Gnomad NFE AF: 0.00181

Gnomad OTH AF: 0.000977

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0582 AC: 63456 AN: 1089660 Hom.: 14 Cov.: 23 AF XY: 0.0606 AC XY: 33187 AN XY: 547650

Gnomad4 AFR exome AF: 0.00897

Gnomad4 AMR exome AF: 0.0244

Gnomad4 ASJ exome AF: 0.0610

Gnomad4 EAS exome AF: 0.00634

Gnomad4 SAS exome AF: 0.0695

Gnomad4 FIN exome AF: 0.0621

Gnomad4 NFE exome AF: 0.0633

Gnomad4 OTH exome AF: 0.0543

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00190 AC: 150 AN: 78866 Hom.: 1 Cov.: 25 AF XY: 0.00250 AC XY: 94 AN XY: 37562

Gnomad4 AFR AF: 0.000482

Gnomad4 AMR AF: 0.000628

Gnomad4 ASJ AF: 0.00509

Gnomad4 EAS AF: 0.0136

Gnomad4 SAS AF: 0.0103

Gnomad4 FIN AF: 0.00344

Gnomad4 NFE AF: 0.00181

Gnomad4 OTH AF: 0.00195

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs66811540; hg19: chr2-46583272;