rs56721780

Positions:

• chr2-46296516-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000460015.1(EPAS1):​n.432+2418G>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,378 control chromosomes in the GnomAD database, including 2,436 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (2435 hom., cov: 32)
  • Exomes 𝑓: 0.070 (1 hom.)
• Consequence: EPAS1 ENST00000460015.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 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	ENST00000460015.1	n.432+2418G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21037 AN: 152132 Hom.: 2413 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.0766

Gnomad FIN AF: 0.0574

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.0703 AC: 9 AN: 128 Hom.: 1 AF XY: 0.0400 AC XY: 4 AN XY: 100

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0761

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.139 AC: 21104 AN: 152250 Hom.: 2435 Cov.: 32 AF XY: 0.136 AC XY: 10088 AN XY: 74450

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.0838

Gnomad4 ASJ AF: 0.0781

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.0765

Gnomad4 FIN AF: 0.0574

Gnomad4 NFE AF: 0.0734

Gnomad4 OTH AF: 0.114

Alfa AF: 0.105 Hom.: 183

Bravo AF: 0.149

Asia WGS AF: 0.0850 AC: 295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.38
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56721780; hg19: chr2-46523655;