rs13391305

chr2-46296782-T-C

Variant summary

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

The ENST00000449347.5(EPAS1):c.-171+57T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 152,228 control chromosomes in the GnomAD database, including 1,265 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 0.074 (1265 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPAS1 ENST00000449347.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 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	ENST00000449347.5	c.-171+57T>C		intron_variant		3
EPAS1	ENST00000460015.1	n.432+2684T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0741 AC: 11271 AN: 152110 Hom.: 1263 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0345

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00867

Gnomad SAS AF: 0.0531

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00310

Gnomad OTH AF: 0.0559

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 70 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 50

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0742 AC: 11292 AN: 152228 Hom.: 1265 Cov.: 33 AF XY: 0.0728 AC XY: 5418 AN XY: 74452

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.0345

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00850

Gnomad4 SAS AF: 0.0528

Gnomad4 FIN AF: 0.000941

Gnomad4 NFE AF: 0.00310

Gnomad4 OTH AF: 0.0553

Alfa AF: 0.0436 Hom.: 77

Bravo AF: 0.0836

Asia WGS AF: 0.0570 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.8
Dann	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13391305; hg19: chr2-46523921;