rs59862329

chr2-46296324-T-C

Variant summary

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

The ENST00000460015.1(EPAS1):n.432+2226T>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 0.118 in 152,138 control chromosomes in the GnomAD database, including 3,424 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 0.12 (3424 hom., cov: 32)
• Consequence: EPAS1 ENST00000460015.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.505

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPAS1	ENST00000460015.1	n.432+2226T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17901 AN: 152020 Hom.: 3419 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00869

Gnomad SAS AF: 0.0530

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00148

Gnomad OTH AF: 0.0828

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.118 AC: 17928 AN: 152138 Hom.: 3424 Cov.: 32 AF XY: 0.114 AC XY: 8448 AN XY: 74360

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.0464

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00852

Gnomad4 SAS AF: 0.0526

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00149

Gnomad4 OTH AF: 0.0819

Alfa AF: 0.0712 Hom.: 296

Bravo AF: 0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	9.9
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs59862329; hg19: chr2-46523463;