rs996347

Variant names:

• chr14-33941686-T-C
• rs996347
• NM_022073.4:c.357+8710A>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.357+8710A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,928 control chromosomes in the GnomAD database, including 6,725 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 0.29 (6725 hom., cov: 32)
• Consequence: EGLN3 NM_022073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.773
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGLN3	NM_022073.4	c.357+8710A>G		intron_variant	Intron 1 of 4	ENST00000250457.9	NP_071356.1
EGLN3	NM_001308103.2	c.75+8992A>G		intron_variant	Intron 1 of 4		NP_001295032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000250457.9	c.357+8710A>G		intron_variant	Intron 1 of 4	1	NM_022073.4	ENSP00000250457.4
EGLN3	ENST00000553215.5	c.75+8992A>G		intron_variant	Intron 1 of 4	1		ENSP00000447470.1
EGLN3	ENST00000487915.6	c.4-10471A>G		intron_variant	Intron 4 of 5	5		ENSP00000451316.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43682 AN: 151810 Hom.: 6722 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.288 AC: 43694 AN: 151928 Hom.: 6725 Cov.: 32 AF XY: 0.281 AC XY: 20889 AN XY: 74232

African (AFR) AF: 0.195 AC: 8087 AN: 41446

American (AMR) AF: 0.219 AC: 3342 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 973 AN: 3466

East Asian (EAS) AF: 0.241 AC: 1243 AN: 5168

South Asian (SAS) AF: 0.189 AC: 911 AN: 4810

European-Finnish (FIN) AF: 0.344 AC: 3609 AN: 10498

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24470 AN: 67956

Other (OTH) AF: 0.275 AC: 580 AN: 2108

Alfa AF: 0.306 Hom.: 9453

Bravo AF: 0.276

Asia WGS AF: 0.241 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.75
DANN	Benign	0.63
PhyloP100		-0.77
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: rs996347; hg19: chr14-34410892;