19-40804666-A-G

Variant names:

• chr19-40804666-A-G
• rs3733829
• NM_080732.4:c.844-1889A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080732.4(EGLN2):​c.844-1889A>G variant causes a intron 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 NM_080732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGLN2	NM_080732.4	c.844-1889A>G		intron_variant	Intron 2 of 5	ENST00000303961.9	NP_542770.2
EGLN2	NM_053046.4	c.844-1889A>G		intron_variant	Intron 2 of 5		NP_444274.1
RAB4B-EGLN2	NR_037791.1	n.1892-1889A>G		intron_variant	Intron 8 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN2	ENST00000303961.9	c.844-1889A>G		intron_variant	Intron 2 of 5	1	NM_080732.4	ENSP00000307080.3
RAB4B-EGLN2	ENST00000594136.2	n.*1093-1889A>G		intron_variant	Intron 8 of 11	2		ENSP00000469872.1
ENSG00000268797	ENST00000601627.1	n.117+3251A>G		intron_variant	Intron 1 of 3	3		ENSP00000469533.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.389

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.0749

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.324

Alfa AF: 0.351 Hom.: 19184

Bravo AF: 0.286

Asia WGS AF: 0.394 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.059
DANN	Benign	0.80

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: rs3733829; hg19: chr19-41310571; COSMIC: COSV58280596; COSMIC: COSV58280596;