rs187545710

Variant names:

• chr19-40799346-G-A
• rs187545710
• NM_080732.4:c.-235+84G>A

Variant summary

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

The NM_080732.4(EGLN2):​c.-235+84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 148,790 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (133 hom., cov: 26)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EGLN2 NM_080732.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.217
• 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=-0.75).
• BP6: Variant 19-40799346-G-A is Benign according to our data. Variant chr19-40799346-G-A is described in ClinVar as Benign. ClinVar VariationId is 1253009.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0701 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080732.4. 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.-235+84G>A		intron	N/A	NP_542770.2	Q96KS0-1
	RAB4B-EGLN2	NR_037791.1		n.815-993G>A		intron	N/A
	EGLN2	NM_053046.4		c.-527G>A		upstream_gene	N/A	NP_444274.1	Q96KS0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN2	ENST00000303961.9	TSL:1 MANE Select	c.-235+84G>A		intron	N/A	ENSP00000307080.3	Q96KS0-1
	RAB4B-EGLN2	ENST00000594136.2	TSL:2	n.*16-993G>A		intron	N/A	ENSP00000469872.1
	EGLN2	ENST00000936252.1		c.-281G>A		5_prime_UTR	Exon 1 of 6	ENSP00000606311.1

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3187 AN: 148682 Hom.: 133 Cov.: 26

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00106

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00645

Gnomad NFE AF: 0.000675

Gnomad OTH AF: 0.0117

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 56 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 42

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0215 AC: 3193 AN: 148790 Hom.: 133 Cov.: 26 AF XY: 0.0206 AC XY: 1495 AN XY: 72666

African (AFR) AF: 0.0723 AC: 2935 AN: 40596

American (AMR) AF: 0.0122 AC: 184 AN: 15050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 4942

South Asian (SAS) AF: 0.000637 AC: 3 AN: 4706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10114

Middle Eastern (MID) AF: 0.00694 AC: 2 AN: 288

European-Non Finnish (NFE) AF: 0.000675 AC: 45 AN: 66704

Other (OTH) AF: 0.0116 AC: 24 AN: 2068

Alfa AF: 0.0158 Hom.: 2

Bravo AF: 0.0247

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	-0.75
CADD	Benign	13
DANN	Benign	0.95
PhyloP100		0.22
PromoterAI		-0.0026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	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: rs187545710; hg19: chr19-41305251;