ENST00000593726.5:c.-246delT

Variant names:

• chr19-40800316-CT-C
• rs35057638
• ENST00000593726.5:c.-246delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000593726.5(EGLN2):​c.-246delT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 384,246 control chromosomes in the GnomAD database, including 8,838 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (6458 hom., cov: 21)
  • Exomes 𝑓: 0.22 (2380 hom.)
• Consequence: EGLN2 ENST00000593726.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.329
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 19-40800316-CT-C is Benign according to our data. Variant chr19-40800316-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1297762.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000593726.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN2	NM_080732.4	MANE Select	c.-234-12delT		intron	N/A	NP_542770.2	Q96KS0-1
	EGLN2	NM_053046.4		c.-234-12delT		intron	N/A	NP_444274.1	Q96KS0-1
	RAB4B-EGLN2	NR_037791.1		n.815-12delT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN2	ENST00000593726.5	TSL:1	c.-246delT		5_prime_UTR	Exon 1 of 5	ENSP00000469686.1	Q96KS0-1
	EGLN2	ENST00000303961.9	TSL:1 MANE Select	c.-234-12delT		intron	N/A	ENSP00000307080.3	Q96KS0-1
	EGLN2	ENST00000406058.6	TSL:1	c.-234-12delT		intron	N/A	ENSP00000385253.1	Q96KS0-1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 36990 AN: 148046 Hom.: 6431 Cov.: 21

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.0348

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0850

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.183

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.224 AC: 52992 AN: 236118 Hom.: 2380 Cov.: 0 AF XY: 0.223 AC XY: 27204 AN XY: 121910

African (AFR) AF: 0.483 AC: 3889 AN: 8058

American (AMR) AF: 0.268 AC: 2494 AN: 9312

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 1683 AN: 7688

East Asian (EAS) AF: 0.205 AC: 3796 AN: 18542

South Asian (SAS) AF: 0.205 AC: 3259 AN: 15926

European-Finnish (FIN) AF: 0.197 AC: 3086 AN: 15680

Middle Eastern (MID) AF: 0.219 AC: 233 AN: 1064

European-Non Finnish (NFE) AF: 0.214 AC: 31148 AN: 145594

Other (OTH) AF: 0.239 AC: 3404 AN: 14254

GnomAD4 genome AF: 0.250 AC: 37059 AN: 148128 Hom.: 6458 Cov.: 21 AF XY: 0.246 AC XY: 17787 AN XY: 72176

African (AFR) AF: 0.501 AC: 20262 AN: 40430

American (AMR) AF: 0.202 AC: 3022 AN: 14930

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 484 AN: 3418

East Asian (EAS) AF: 0.0850 AC: 431 AN: 5068

South Asian (SAS) AF: 0.168 AC: 786 AN: 4684

European-Finnish (FIN) AF: 0.143 AC: 1385 AN: 9718

Middle Eastern (MID) AF: 0.189 AC: 54 AN: 286

European-Non Finnish (NFE) AF: 0.152 AC: 10149 AN: 66674

Other (OTH) AF: 0.224 AC: 455 AN: 2028

Alfa AF: 0.0623 Hom.: 69

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35057638; hg19: chr19-41306221; COSMIC: COSV58281473; COSMIC: COSV58281473;