14-34013320-A-G

Variant names:

• chr14-34013320-A-G
• rs1471639
• ENST00000487915.6:c.3+79001T>C

Variant summary

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

The ENST00000550114.5(EGLN3):​n.55+5281T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,112 control chromosomes in the GnomAD database, including 5,563 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 0.26 (5563 hom., cov: 32)
• Consequence: EGLN3 ENST00000550114.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425
• Publications: 3 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]

LOC102724945 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000550114.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN3	ENST00000487915.6	TSL:5	c.3+79001T>C		intron	N/A	ENSP00000451316.1	G3V3M1
	EGLN3	ENST00000550114.5	TSL:4	n.55+5281T>C		intron	N/A
	EGLN3	ENST00000551935.5	TSL:4	n.298-26158T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40258 AN: 151994 Hom.: 5561 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.265 AC: 40285 AN: 152112 Hom.: 5563 Cov.: 32 AF XY: 0.260 AC XY: 19303 AN XY: 74362

African (AFR) AF: 0.292 AC: 12129 AN: 41468

American (AMR) AF: 0.227 AC: 3464 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3470

East Asian (EAS) AF: 0.293 AC: 1519 AN: 5176

South Asian (SAS) AF: 0.180 AC: 871 AN: 4826

European-Finnish (FIN) AF: 0.227 AC: 2406 AN: 10584

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18170 AN: 67982

Other (OTH) AF: 0.238 AC: 502 AN: 2112

Alfa AF: 0.197 Hom.: 634

Bravo AF: 0.272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.55
PhyloP100		-0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1471639;

hg19: chr14-34482526;