chr2-46327394-C-G

Position:

• chr2-46327394-C-G

Variant summary

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

The NM_001430.5(EPAS1):​c.27-19479C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,806 control chromosomes in the GnomAD database, including 17,344 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 0.48 (17344 hom., cov: 31)
• Consequence: EPAS1 NM_001430.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPAS1	NM_001430.5	c.27-19479C>G		intron_variant		ENST00000263734.5
EPAS1	XM_011532698.3	c.65+1518C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPAS1	ENST00000263734.5	c.27-19479C>G		intron_variant		1	NM_001430.5	P1
EPAS1	ENST00000449347.5	c.27-19479C>G		intron_variant		3
EPAS1	ENST00000460015.1	n.433-19479C>G		intron_variant, non_coding_transcript_variant		4
EPAS1	ENST00000467888.5	n.175-19479C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72113 AN: 151690 Hom.: 17322 Cov.: 31

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.475 AC: 72180 AN: 151806 Hom.: 17344 Cov.: 31 AF XY: 0.479 AC XY: 35515 AN XY: 74168

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.465

Alfa AF: 0.284 Hom.: 599

Bravo AF: 0.487

Asia WGS AF: 0.557 AC: 1936 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.072
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11125071; hg19: chr2-46554533;