14-34011308-C-T

Variant names:

• chr14-34011308-C-T
• rs974673
• ENST00000487915.6:c.4-80093G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000487915.6(EGLN3):​c.4-80093G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,214 control chromosomes in the GnomAD database, including 1,572 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 0.13 (1572 hom., cov: 33)
• Consequence: EGLN3 ENST00000487915.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.720

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC102724945	XR_001750942.2	n.484-24146G>A		intron_variant	Intron 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000487915.6	c.4-80093G>A		intron_variant	Intron 4 of 5	5		ENSP00000451316.1
EGLN3	ENST00000550114.5	n.55+7293G>A		intron_variant	Intron 1 of 2	4
EGLN3	ENST00000551935.5	n.298-24146G>A		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20056 AN: 152094 Hom.: 1572 Cov.: 33

Gnomad AFR AF: 0.0598

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.0882

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.132 AC: 20060 AN: 152214 Hom.: 1572 Cov.: 33 AF XY: 0.133 AC XY: 9870 AN XY: 74418

Gnomad4 AFR AF: 0.0597

Gnomad4 AMR AF: 0.0881

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.137

Alfa AF: 0.150 Hom.: 2504

Bravo AF: 0.124

Asia WGS AF: 0.204 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs974673; hg19: chr14-34480514;