Variant 19-40800457-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_080732.4(EGLN2):c.-116G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,425,032 control chromosomes in the GnomAD database, including 88,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7791 hom., cov: 32)

Exomes 𝑓: 0.35 ( 80640 hom. )

Consequence

EGLN2
NM_080732.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.534

Variant links:

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]

EGLN2 links:

RAB4B-EGLN2 (HGNC:):

RAB4B-EGLN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 19-40800457-G-A is Benign according to our data. Variant chr19-40800457-G-A is described in ClinVar as [Benign]. Clinvar id is 1283246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
EGLN2	NM_080732.4 linkuse as main transcript	c.-116G>A	5_prime_UTR_variant	2/6	ENST00000303961.9	NP_542770.2
RAB4B-EGLN2	NR_037791.1 linkuse as main transcript	n.933G>A	non_coding_transcript_exon_variant	8/12
EGLN2	NM_053046.4 linkuse as main transcript	c.-116G>A	5_prime_UTR_variant	2/6		NP_444274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN2	ENST00000303961.9 linkuse as main transcript	c.-116G>A		5_prime_UTR_variant	2/6	1	NM_080732.4	ENSP00000307080	P1	Q96KS0-1

Frequencies

GnomAD3 genomes

AF:

0.286

AC:

43464

AN:

151830

Hom.:

7784

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0729

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.425

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.357

Gnomad OTH

AF:

0.316

GnomAD4 exome

AF:

0.351

AC:

447178

AN:

1273084

Hom.:

80640

Cov.:

AF XY:

0.353

AC XY:

218371

AN XY:

618942

show subpopulations

Gnomad4 AFR exome

AF:

0.0569

Gnomad4 AMR exome

AF:

0.476

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.383

Gnomad4 SAS exome

AF:

0.377

Gnomad4 FIN exome

AF:

0.359

Gnomad4 NFE exome

AF:

0.356

Gnomad4 OTH exome

AF:

0.340

GnomAD4 genome

AF:

0.286

AC:

43482

AN:

151948

Hom.:

7791

Cov.:

AF XY:

0.289

AC XY:

21490

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.0728

Gnomad4 AMR

AF:

0.425

Gnomad4 ASJ

AF:

0.298

Gnomad4 EAS

AF:

0.371

Gnomad4 SAS

AF:

0.378

Gnomad4 FIN

AF:

0.358

Gnomad4 NFE

AF:

0.357

Gnomad4 OTH

AF:

0.321

Alfa

AF:

0.291

Hom.:

918

Bravo

AF:

0.282

Asia WGS

AF:

0.395

AC:

1372

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.6

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over