2-46362348-C-G

Variant names:

• chr2-46362348-C-G
• rs13412887
• NM_001430.5:c.779+1258C>G

Variant summary

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

The NM_001430.5(EPAS1):​c.779+1258C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,192 control chromosomes in the GnomAD database, including 2,083 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 0.15 (2083 hom., cov: 32)
• Consequence: EPAS1 NM_001430.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.218 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.779+1258C>G		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.779+1258C>G		intron	N/A	ENSP00000263734.3	Q99814
	EPAS1	ENST00000861819.1		c.779+1258C>G		intron	N/A	ENSP00000531878.1
	EPAS1	ENST00000861817.1		c.773+1258C>G		intron	N/A	ENSP00000531876.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22452 AN: 152072 Hom.: 2077 Cov.: 32

Gnomad AFR AF: 0.0376

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.148 AC: 22467 AN: 152192 Hom.: 2083 Cov.: 32 AF XY: 0.150 AC XY: 11134 AN XY: 74392

African (AFR) AF: 0.0375 AC: 1558 AN: 41542

American (AMR) AF: 0.225 AC: 3436 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 657 AN: 3470

East Asian (EAS) AF: 0.169 AC: 876 AN: 5174

South Asian (SAS) AF: 0.126 AC: 606 AN: 4822

European-Finnish (FIN) AF: 0.206 AC: 2174 AN: 10576

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12624 AN: 67992

Other (OTH) AF: 0.176 AC: 371 AN: 2110

Alfa AF: 0.103 Hom.: 187

Bravo AF: 0.144

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.62
DANN	Benign	0.43
PhyloP100		-0.030
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: rs13412887; hg19: chr2-46589487;