19-40800164-C-T

Position:

• chr19-40800164-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000303961.9(EGLN2):​c.-234-175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 199,708 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (106 hom., cov: 30)
  • Exomes 𝑓: 0.0030 (1 hom.)
• Consequence: EGLN2 ENST00000303961.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.68

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:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-40800164-C-T is Benign according to our data. Variant chr19-40800164-C-T is described in ClinVar as [Benign]. Clinvar id is 1291782.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGLN2	NM_080732.4	c.-234-175C>T		intron_variant		ENST00000303961.9	NP_542770.2
RAB4B-EGLN2	NR_037791.1	n.815-175C>T		intron_variant, non_coding_transcript_variant
EGLN2	NM_053046.4	c.-234-175C>T		intron_variant			NP_444274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN2	ENST00000303961.9	c.-234-175C>T		intron_variant		1	NM_080732.4	ENSP00000307080	P1

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 3007 AN: 152022 Hom.: 106 Cov.: 30

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00301 AC: 143 AN: 47568 Hom.: 1 Cov.: 0 AF XY: 0.00285 AC XY: 73 AN XY: 25584

Gnomad4 AFR exome AF: 0.0511

Gnomad4 AMR exome AF: 0.00718

Gnomad4 ASJ exome AF: 0.000933

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000158

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000577

Gnomad4 OTH exome AF: 0.00668

GnomAD4 genome AF: 0.0198 AC: 3012 AN: 152140 Hom.: 106 Cov.: 30 AF XY: 0.0189 AC XY: 1409 AN XY: 74390

Gnomad4 AFR AF: 0.0667

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000677

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0149 Hom.: 2

Bravo AF: 0.0226

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.75

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: rs76268776; hg19: chr19-41306069;