rs7589621

Variant names:

• chr2-46355243-G-A
• rs7589621
• NM_001430.5:c.218-908G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-46355243-G-A
• chr2-46355243-G-T

Variant summary

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

The NM_001430.5(EPAS1):​c.218-908G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,086 control chromosomes in the GnomAD database, including 9,310 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 0.33 (9310 hom., cov: 32)
• Consequence: EPAS1 NM_001430.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504
• Publications: 12 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001430.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPAS1	NM_001430.5	MANE Select	c.218-908G>A		intron	N/A	NP_001421.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPAS1	ENST00000263734.5	TSL:1 MANE Select	c.218-908G>A		intron	N/A	ENSP00000263734.3	Q99814
	EPAS1	ENST00000861819.1		c.218-908G>A		intron	N/A	ENSP00000531878.1
	EPAS1	ENST00000861817.1		c.212-908G>A		intron	N/A	ENSP00000531876.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50537 AN: 151968 Hom.: 9283 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.333 AC: 50594 AN: 152086 Hom.: 9310 Cov.: 32 AF XY: 0.338 AC XY: 25145 AN XY: 74350

African (AFR) AF: 0.388 AC: 16079 AN: 41484

American (AMR) AF: 0.368 AC: 5628 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 883 AN: 3472

East Asian (EAS) AF: 0.768 AC: 3978 AN: 5178

South Asian (SAS) AF: 0.317 AC: 1527 AN: 4824

European-Finnish (FIN) AF: 0.303 AC: 3197 AN: 10562

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18089 AN: 67958

Other (OTH) AF: 0.336 AC: 710 AN: 2110

Alfa AF: 0.293 Hom.: 14848

Bravo AF: 0.341

Asia WGS AF: 0.534 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.36
DANN	Benign	0.42
PhyloP100		-0.50
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: rs7589621; hg19: chr2-46582382;