2-46297264-G-C

Position:

• chr2-46297264-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000449347.5(EPAS1):​c.-170-478G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 149,410 control chromosomes in the GnomAD database, including 1,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (1209 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPAS1 ENST00000449347.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.980

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-46297264-G-C is Benign according to our data. Variant chr2-46297264-G-C is described in ClinVar as [Benign]. Clinvar id is 1275431.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.46297264G>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPAS1	ENST00000449347.5	c.-170-478G>C		intron_variant		3		ENSP00000406137.1
EPAS1	ENST00000460015.1	n.432+3166G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 10926 AN: 149302 Hom.: 1201 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.00117

Gnomad EAS AF: 0.0101

Gnomad SAS AF: 0.0551

Gnomad FIN AF: 0.000934

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00306

Gnomad OTH AF: 0.0550

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0734 AC: 10960 AN: 149410 Hom.: 1209 Cov.: 32 AF XY: 0.0723 AC XY: 5273 AN XY: 72912

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.0335

Gnomad4 ASJ AF: 0.00117

Gnomad4 EAS AF: 0.00990

Gnomad4 SAS AF: 0.0549

Gnomad4 FIN AF: 0.000934

Gnomad4 NFE AF: 0.00306

Gnomad4 OTH AF: 0.0544

Alfa AF: 0.0428 Hom.: 77

Bravo AF: 0.0816

Asia WGS AF: 0.0560 AC: 188 AN: 3392

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

GeneDx

Jun 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.9
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs184614491; hg19: chr2-46524403;