14-34227705-C-T

Variant names:

• chr14-34227705-C-T
• rs1244362
• ENST00000546681.5:n.56+54G>A

Variant summary

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

The ENST00000551935.5(EGLN3):​n.60-58059G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,010 control chromosomes in the GnomAD database, including 9,504 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 0.34 (9504 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: EGLN3 ENST00000551935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000546681.5	n.56+54G>A		intron_variant	Intron 1 of 3	5
EGLN3	ENST00000551935.5	n.60-58059G>A		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50903 AN: 151894 Hom.: 9466 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.335 AC: 50997 AN: 152010 Hom.: 9504 Cov.: 32 AF XY: 0.341 AC XY: 25333 AN XY: 74288

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.308

Alfa AF: 0.293 Hom.: 847

Bravo AF: 0.351

Asia WGS AF: 0.489 AC: 1700 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	2.1
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1244362; hg19: chr14-34696911;