14-34006606-G-C

Variant names:

• chr14-34006606-G-C
• rs1626390
• ENST00000487915.6:c.4-75391C>G

Variant summary

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

The ENST00000550114.5(EGLN3):​n.55+11995C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 152,020 control chromosomes in the GnomAD database, including 59,974 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 0.89 (59974 hom., cov: 29)
• Consequence: EGLN3 ENST00000550114.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 1 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.904 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.4-75391C>G		intron	N/A	ENSP00000451316.1	G3V3M1
	EGLN3	ENST00000550114.5	TSL:4	n.55+11995C>G		intron	N/A
	EGLN3	ENST00000551935.5	TSL:4	n.298-19444C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134746 AN: 151902 Hom.: 59931 Cov.: 29

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.863

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.860

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

GnomAD4 genome AF: 0.887 AC: 134847 AN: 152020 Hom.: 59974 Cov.: 29 AF XY: 0.888 AC XY: 65958 AN XY: 74282

African (AFR) AF: 0.912 AC: 37801 AN: 41468

American (AMR) AF: 0.783 AC: 11950 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3072 AN: 3466

East Asian (EAS) AF: 0.898 AC: 4644 AN: 5170

South Asian (SAS) AF: 0.915 AC: 4389 AN: 4798

European-Finnish (FIN) AF: 0.919 AC: 9694 AN: 10552

Middle Eastern (MID) AF: 0.863 AC: 252 AN: 292

European-Non Finnish (NFE) AF: 0.889 AC: 60479 AN: 67996

Other (OTH) AF: 0.859 AC: 1810 AN: 2106

Alfa AF: 0.897 Hom.: 7145

Bravo AF: 0.875

Asia WGS AF: 0.867 AC: 3015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.55
PhyloP100		-0.033

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: rs1626390;

hg19: chr14-34475812;