rs9973653

Positions:

• chr2-46320970-G-T

Variant summary

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

The NM_001430.5(EPAS1):​c.26+23033G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,010 control chromosomes in the GnomAD database, including 14,503 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 0.41 (14503 hom., cov: 33)
• Consequence: EPAS1 NM_001430.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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]

EPAS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPAS1	NM_001430.5	c.26+23033G>T		intron_variant		ENST00000263734.5	NP_001421.2
EPAS1	XM_011532698.3	c.-4842G>T		5_prime_UTR_variant	1/16		XP_011531000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPAS1	ENST00000263734.5	c.26+23033G>T		intron_variant		1	NM_001430.5	ENSP00000263734.3
EPAS1	ENST00000449347.5	c.26+23033G>T		intron_variant		3		ENSP00000406137.1
EPAS1	ENST00000460015.1	n.433-25903G>T		intron_variant		4
EPAS1	ENST00000467888.5	n.174+23033G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62553 AN: 151892 Hom.: 14488 Cov.: 33

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.412 AC: 62618 AN: 152010 Hom.: 14503 Cov.: 33 AF XY: 0.413 AC XY: 30643 AN XY: 74266

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.385

Alfa AF: 0.317 Hom.: 11045

Bravo AF: 0.424

Asia WGS AF: 0.457 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.097
DANN	Benign	0.37

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: rs9973653; hg19: chr2-46548109;