2-46327394-C-G

Variant summary

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

The NM_001430.5(EPAS1):​c.27-19479C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,806 control chromosomes in the GnomAD database, including 17,344 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 0.48 ( 17344 hom., cov: 31)

Consequence

EPAS1
NM_001430.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14
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=-1.0).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EPAS1NM_001430.5 linkuse as main transcriptc.27-19479C>G intron_variant ENST00000263734.5
EPAS1XM_011532698.3 linkuse as main transcriptc.65+1518C>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EPAS1ENST00000263734.5 linkuse as main transcriptc.27-19479C>G intron_variant 1 NM_001430.5 P1
EPAS1ENST00000449347.5 linkuse as main transcriptc.27-19479C>G intron_variant 3
EPAS1ENST00000460015.1 linkuse as main transcriptn.433-19479C>G intron_variant, non_coding_transcript_variant 4
EPAS1ENST00000467888.5 linkuse as main transcriptn.175-19479C>G intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.475
AC:
72113
AN:
151690
Hom.:
17322
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.484
Gnomad AMI
AF:
0.357
Gnomad AMR
AF:
0.577
Gnomad ASJ
AF:
0.407
Gnomad EAS
AF:
0.656
Gnomad SAS
AF:
0.436
Gnomad FIN
AF:
0.481
Gnomad MID
AF:
0.399
Gnomad NFE
AF:
0.442
Gnomad OTH
AF:
0.461
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.475
AC:
72180
AN:
151806
Hom.:
17344
Cov.:
31
AF XY:
0.479
AC XY:
35515
AN XY:
74168
show subpopulations
Gnomad4 AFR
AF:
0.484
Gnomad4 AMR
AF:
0.577
Gnomad4 ASJ
AF:
0.407
Gnomad4 EAS
AF:
0.656
Gnomad4 SAS
AF:
0.436
Gnomad4 FIN
AF:
0.481
Gnomad4 NFE
AF:
0.442
Gnomad4 OTH
AF:
0.465
Alfa
AF:
0.284
Hom.:
599
Bravo
AF:
0.487
Asia WGS
AF:
0.557
AC:
1936
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.072
DANN
Benign
0.29

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: rs11125071; hg19: chr2-46554533; API