2-46297561-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001430.5(EPAS1):c.-341dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 290,088 control chromosomes in the GnomAD database, including 1,012 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.066 (1007 hom., cov: 31)
  • Exomes 𝑓: 0.046 (5 hom.)
• Consequence: EPAS1 NM_001430.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.788

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-46297561-C-CT is Benign according to our data. Variant chr2-46297561-C-CT is described in ClinVar as [Benign]. Clinvar id is 336221.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPAS1	NM_001430.5	c.-341dup		5_prime_UTR_variant	1/16	ENST00000263734.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPAS1	ENST00000263734.5	c.-341dup		5_prime_UTR_variant	1/16	1	NM_001430.5	P1
EPAS1	ENST00000449347.5	c.-170-171dup		intron_variant		3
EPAS1	ENST00000460015.1	n.432+3473dup		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 9866 AN: 149400 Hom.: 1004 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0311

Gnomad ASJ AF: 0.00146

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00126

Gnomad FIN AF: 0.00111

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00310

Gnomad OTH AF: 0.0523

GnomAD4 exome AF: 0.0464 AC: 6518 AN: 140592 Hom.: 5 Cov.: 0 AF XY: 0.0457 AC XY: 3562 AN XY: 77962

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.0604

Gnomad4 ASJ exome AF: 0.0449

Gnomad4 EAS exome AF: 0.0525

Gnomad4 SAS exome AF: 0.0413

Gnomad4 FIN exome AF: 0.0400

Gnomad4 NFE exome AF: 0.0437

Gnomad4 OTH exome AF: 0.0519

GnomAD4 genome AF: 0.0661 AC: 9877 AN: 149496 Hom.: 1007 Cov.: 31 AF XY: 0.0643 AC XY: 4688 AN XY: 72944

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.0311

Gnomad4 ASJ AF: 0.00146

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00126

Gnomad4 FIN AF: 0.00111

Gnomad4 NFE AF: 0.00310

Gnomad4 OTH AF: 0.0518

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial erythrocytosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs149642079; hg19: chr2-46524700;