chr14-34034445-G-T

Variant names:

• chr14-34034445-G-T
• rs1680730
• ENST00000487915.6:c.3+57876C>A

Variant summary

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

The ENST00000487915.6(EGLN3):​c.3+57876C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 151,770 control chromosomes in the GnomAD database, including 57,376 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 0.87 (57376 hom., cov: 29)
• Consequence: EGLN3 ENST00000487915.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC102724945	XR_001750942.2	n.484-47283C>A		intron_variant	Intron 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000487915.6	c.3+57876C>A		intron_variant	Intron 4 of 5	5		ENSP00000451316.1
EGLN3	ENST00000551935.5	n.298-47283C>A		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.868 AC: 131600 AN: 151652 Hom.: 57337 Cov.: 29

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.929

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.889

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

GnomAD4 genome AF: 0.868 AC: 131693 AN: 151770 Hom.: 57376 Cov.: 29 AF XY: 0.868 AC XY: 64376 AN XY: 74128

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.928

Gnomad4 ASJ AF: 0.929

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.885

Gnomad4 FIN AF: 0.901

Gnomad4 NFE AF: 0.898

Gnomad4 OTH AF: 0.889

Alfa AF: 0.897 Hom.: 76221

Bravo AF: 0.864

Asia WGS AF: 0.865 AC: 3006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1680730; hg19: chr14-34503651;