NM_022073.4:c.358-683A>G

Variant names:

• chr14-33931898-T-C
• rs1032015
• NM_022073.4:c.358-683A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022073.4(EGLN3):​c.358-683A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,144 control chromosomes in the GnomAD database, including 9,938 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 0.35 (9938 hom., cov: 33)
• Consequence: EGLN3 NM_022073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 4 publications found

Genes affected

EGLN3 (HGNC:14661): (egl-9 family hypoxia inducible factor 3) Enables peptidyl-proline 4-dioxygenase activity. Involved in several processes, including activation of cysteine-type endopeptidase activity involved in apoptotic process; peptidyl-proline hydroxylation to 4-hydroxy-L-proline; and response to hypoxia. Located in cytosol and nucleus. Implicated in renal cell carcinoma. Biomarker of clear cell renal cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022073.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN3	NM_022073.4	MANE Select	c.358-683A>G		intron	N/A	NP_071356.1
	EGLN3	NM_001308103.2		c.76-683A>G		intron	N/A	NP_001295032.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN3	ENST00000250457.9	TSL:1 MANE Select	c.358-683A>G		intron	N/A	ENSP00000250457.4
	EGLN3	ENST00000553215.5	TSL:1	c.76-683A>G		intron	N/A	ENSP00000447470.1
	EGLN3	ENST00000487915.6	TSL:5	c.4-683A>G		intron	N/A	ENSP00000451316.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52488 AN: 152026 Hom.: 9936 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.336

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.345 AC: 52494 AN: 152144 Hom.: 9938 Cov.: 33 AF XY: 0.336 AC XY: 25023 AN XY: 74364

African (AFR) AF: 0.220 AC: 9134 AN: 41508

American (AMR) AF: 0.269 AC: 4109 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1215 AN: 3472

East Asian (EAS) AF: 0.285 AC: 1476 AN: 5178

South Asian (SAS) AF: 0.258 AC: 1243 AN: 4820

European-Finnish (FIN) AF: 0.395 AC: 4176 AN: 10572

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29958 AN: 68002

Other (OTH) AF: 0.339 AC: 717 AN: 2112

Alfa AF: 0.404 Hom.: 53816

Bravo AF: 0.332

Asia WGS AF: 0.300 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.6
DANN	Benign	0.62
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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: rs1032015; hg19: chr14-34401104;