ENST00000593445.5:n.197A>G

Variant names:

• chr19-40804666-A-G
• rs3733829
• ENST00000593445.5:n.197A>G

Variant summary

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

The ENST00000593445.5(EGLN2):​n.197A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,242 control chromosomes in the GnomAD database, including 7,948 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 0.29 (7938 hom., cov: 32)
  • Exomes 𝑓: 0.30 (10 hom.)
• Consequence: EGLN2 ENST00000593445.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• Publications: 82 publications found

Genes affected

EGLN2 (HGNC:14660): (egl-9 family hypoxia inducible factor 2) The hypoxia inducible factor (HIF) is a transcriptional complex that is involved in oxygen homeostasis. At normal oxygen levels, the alpha subunit of HIF is targeted for degration by prolyl hydroxylation. This gene encodes an enzyme responsible for this post-translational modification. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream RAB4B (RAB4B, member RAS oncogene family) gene. [provided by RefSeq, Feb 2011]

RAB4B-EGLN2 (HGNC:44465): (RAB4B-EGLN2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring RAB4B (RAB4B, member RAS oncogene family) and EGLN2 (egl nine homolog 2) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ENSG00000268797 (HGNC:):

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 = 0.421 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000593445.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN2	NM_080732.4	MANE Select	c.844-1889A>G		intron	N/A	NP_542770.2
	EGLN2	NM_053046.4		c.844-1889A>G		intron	N/A	NP_444274.1
	RAB4B-EGLN2	NR_037791.1		n.1892-1889A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN2	ENST00000593445.5	TSL:1	n.197A>G		non_coding_transcript_exon	Exon 1 of 4
	EGLN2	ENST00000303961.9	TSL:1 MANE Select	c.844-1889A>G		intron	N/A	ENSP00000307080.3
	EGLN2	ENST00000406058.6	TSL:1	c.844-1889A>G		intron	N/A	ENSP00000385253.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43958 AN: 151986 Hom.: 7931 Cov.: 32

Gnomad AFR AF: 0.0751

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.304 AC: 42 AN: 138 Hom.: 10 Cov.: 0 AF XY: 0.316 AC XY: 31 AN XY: 98

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.667 AC: 4 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.389 AC: 7 AN: 18

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.341 AC: 30 AN: 88

Other (OTH) AF: 0.00 AC: 0 AN: 12

GnomAD4 genome AF: 0.289 AC: 43977 AN: 152104 Hom.: 7938 Cov.: 32 AF XY: 0.292 AC XY: 21698 AN XY: 74330

African (AFR) AF: 0.0749 AC: 3109 AN: 41504

American (AMR) AF: 0.430 AC: 6570 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3470

East Asian (EAS) AF: 0.373 AC: 1926 AN: 5164

South Asian (SAS) AF: 0.378 AC: 1825 AN: 4826

European-Finnish (FIN) AF: 0.359 AC: 3794 AN: 10570

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24516 AN: 67966

Other (OTH) AF: 0.324 AC: 685 AN: 2112

Alfa AF: 0.340 Hom.: 40256

Bravo AF: 0.286

Asia WGS AF: 0.394 AC: 1369 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	0.059
DANN	Benign	0.80
PhyloP100		-2.7
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: rs3733829; hg19: chr19-41310571; COSMIC: COSV58280596; COSMIC: COSV58280596;