2-46356133-ACCC-A

Position:

• chr2-46356133-ACCC-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000263734.5(EPAS1):​c.218-10_218-8delCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,139,244 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.00013 (0 hom.)
• 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 -6 ACMG points.

• BP6: Variant 2-46356133-ACCC-A is Benign according to our data. Variant chr2-46356133-ACCC-A is described in ClinVar as [Benign]. Clinvar id is 2776122.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 149 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPAS1	NM_001430.5	c.218-10_218-8delCCC		splice_region_variant, intron_variant		ENST00000263734.5	NP_001421.2
EPAS1	XM_011532698.3	c.257-10_257-8delCCC		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.218-10_218-8delCCC		splice_region_variant, intron_variant		1	NM_001430.5	ENSP00000263734.3
EPAS1	ENST00000449347.5	c.218-10_218-8delCCC		splice_region_variant, intron_variant		3		ENSP00000406137.1
EPAS1	ENST00000463191.1	n.27_29delCCC		non_coding_transcript_exon_variant	1/4	2
EPAS1	ENST00000475822.1	n.409-10_409-8delCCC		splice_region_variant, intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.000131 AC: 149 AN: 1139244 Hom.: 0 AF XY: 0.000118 AC XY: 68 AN XY: 574048

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000454

Gnomad4 EAS exome AF: 0.0000261

Gnomad4 SAS exome AF: 0.0000262

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000172

Gnomad4 OTH exome AF: 0.0000413

GnomAD4 genome Cov.: 25

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 17, 2024

- -

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-46583272;