19-40800164-C-T

Variant names:

• chr19-40800164-C-T
• rs76268776
• ENST00000593726.5:c.-409C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000593726.5(EGLN2):​c.-409C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 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 ENST00000593726.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.68
• Publications: 1 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 -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 VariationId 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.

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.-234-175C>T		intron	N/A	NP_542770.2	Q96KS0-1
	EGLN2	NM_053046.4		c.-234-175C>T		intron	N/A	NP_444274.1	Q96KS0-1
	RAB4B-EGLN2	NR_037791.1		n.815-175C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN2	ENST00000593726.5	TSL:1	c.-409C>T		5_prime_UTR	Exon 1 of 5	ENSP00000469686.1	Q96KS0-1
	EGLN2	ENST00000303961.9	TSL:1 MANE Select	c.-234-175C>T		intron	N/A	ENSP00000307080.3	Q96KS0-1
	EGLN2	ENST00000406058.6	TSL:1	c.-234-175C>T		intron	N/A	ENSP00000385253.1	Q96KS0-1

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

African (AFR) AF: 0.0511 AC: 80 AN: 1566

American (AMR) AF: 0.00718 AC: 27 AN: 3758

Ashkenazi Jewish (ASJ) AF: 0.000933 AC: 1 AN: 1072

East Asian (EAS) AF: 0.00 AC: 0 AN: 2904

South Asian (SAS) AF: 0.000158 AC: 1 AN: 6326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1648

Middle Eastern (MID) AF: 0.0119 AC: 2 AN: 168

European-Non Finnish (NFE) AF: 0.000577 AC: 16 AN: 27730

Other (OTH) AF: 0.00668 AC: 16 AN: 2396

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

African (AFR) AF: 0.0667 AC: 2770 AN: 41502

American (AMR) AF: 0.0111 AC: 170 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000677 AC: 46 AN: 67992

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.0282 Hom.: 32

Bravo AF: 0.0226

Asia WGS AF: 0.00577 AC: 20 AN: 3478

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
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.75
PhyloP100		-1.7
PromoterAI		-0.011	Neutral
Mutation Taster		=100/0	polymorphism

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: rs76268776; hg19: chr19-41306069;