rs1374749

Variant names:

• chr2-46369294-G-A
• rs1374749
• NM_001430.5:c.780-533G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-46369294-G-A
• chr2-46369294-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001430.5(EPAS1):​c.780-533G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,966 control chromosomes in the GnomAD database, including 19,866 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 0.50 (19866 hom., cov: 32)
• Consequence: EPAS1 NM_001430.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 9 publications found

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]

LINC01820 (HGNC:52625): (long intergenic non-protein coding RNA 1820)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPAS1	NM_001430.5	c.780-533G>A		intron_variant	Intron 6 of 15	ENST00000263734.5	NP_001421.2
EPAS1	XM_011532698.3	c.819-533G>A		intron_variant	Intron 6 of 15		XP_011531000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPAS1	ENST00000263734.5	c.780-533G>A		intron_variant	Intron 6 of 15	1	NM_001430.5	ENSP00000263734.3
LINC01820	ENST00000843948.1	n.103-21235C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76559 AN: 151848 Hom.: 19825 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.504 AC: 76650 AN: 151966 Hom.: 19866 Cov.: 32 AF XY: 0.514 AC XY: 38140 AN XY: 74266

African (AFR) AF: 0.488 AC: 20214 AN: 41424

American (AMR) AF: 0.637 AC: 9723 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1640 AN: 3470

East Asian (EAS) AF: 0.811 AC: 4188 AN: 5164

South Asian (SAS) AF: 0.543 AC: 2613 AN: 4808

European-Finnish (FIN) AF: 0.522 AC: 5510 AN: 10548

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 31013 AN: 67974

Other (OTH) AF: 0.516 AC: 1087 AN: 2108

Alfa AF: 0.476 Hom.: 41697

Bravo AF: 0.512

Asia WGS AF: 0.645 AC: 2243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.45
DANN	Benign	0.45
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1374749; hg19: chr2-46596433;