rs59862329

Variant names:

• chr2-46296324-T-C
• rs59862329
• ENST00000460015.1:n.432+2226T>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 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
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPAS1	ENST00000460015.1	n.432+2226T>C		intron_variant	Intron 1 of 1	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;