14-34117457-C-T

Variant names:

• chr14-34117457-C-T
• rs2027338
• ENST00000487915.6:c.-79-25055G>A

Variant summary

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

The ENST00000548285.5(EGLN3):​n.449+8796G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,042 control chromosomes in the GnomAD database, including 24,499 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 0.57 (24499 hom., cov: 32)
• Consequence: EGLN3 ENST00000548285.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000548285.5. 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.-79-25055G>A		intron	N/A	ENSP00000451316.1	G3V3M1
	EGLN3	ENST00000546681.5	TSL:5	n.328+9572G>A		intron	N/A
	EGLN3	ENST00000548285.5	TSL:3	n.449+8796G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86246 AN: 151924 Hom.: 24485 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.568 AC: 86311 AN: 152042 Hom.: 24499 Cov.: 32 AF XY: 0.568 AC XY: 42223 AN XY: 74318

African (AFR) AF: 0.559 AC: 23159 AN: 41456

American (AMR) AF: 0.649 AC: 9920 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2036 AN: 3464

East Asian (EAS) AF: 0.465 AC: 2400 AN: 5160

South Asian (SAS) AF: 0.584 AC: 2813 AN: 4814

European-Finnish (FIN) AF: 0.563 AC: 5942 AN: 10560

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38151 AN: 67976

Other (OTH) AF: 0.561 AC: 1185 AN: 2114

Alfa AF: 0.571 Hom.: 3077

Bravo AF: 0.573

Asia WGS AF: 0.499 AC: 1736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.52
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs2027338; hg19: chr14-34586663;