rs6706003

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000263734.5(EPAS1):​c.27-10620C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,082 control chromosomes in the GnomAD database, including 34,326 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 0.64 ( 34326 hom., cov: 31)

Consequence

EPAS1
ENST00000263734.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.26
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EPAS1NM_001430.5 linkuse as main transcriptc.27-10620C>G intron_variant ENST00000263734.5 NP_001421.2
EPAS1XM_011532698.3 linkuse as main transcriptc.65+10377C>G intron_variant XP_011531000.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EPAS1ENST00000263734.5 linkuse as main transcriptc.27-10620C>G intron_variant 1 NM_001430.5 ENSP00000263734 P1

Frequencies

GnomAD3 genomes
AF:
0.644
AC:
97857
AN:
151964
Hom.:
34261
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.902
Gnomad AMI
AF:
0.652
Gnomad AMR
AF:
0.692
Gnomad ASJ
AF:
0.536
Gnomad EAS
AF:
0.963
Gnomad SAS
AF:
0.623
Gnomad FIN
AF:
0.509
Gnomad MID
AF:
0.491
Gnomad NFE
AF:
0.482
Gnomad OTH
AF:
0.606
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.644
AC:
97981
AN:
152082
Hom.:
34326
Cov.:
31
AF XY:
0.648
AC XY:
48146
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.902
Gnomad4 AMR
AF:
0.692
Gnomad4 ASJ
AF:
0.536
Gnomad4 EAS
AF:
0.963
Gnomad4 SAS
AF:
0.621
Gnomad4 FIN
AF:
0.509
Gnomad4 NFE
AF:
0.482
Gnomad4 OTH
AF:
0.610
Alfa
AF:
0.556
Hom.:
3191
Bravo
AF:
0.674
Asia WGS
AF:
0.809
AC:
2813
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.040
DANN
Benign
0.24

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6706003; hg19: chr2-46563392; API