ENST00000487915.6:c.3+57876C>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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 = 0.915 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000487915.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN3	ENST00000487915.6	TSL:5	c.3+57876C>A		intron	N/A	ENSP00000451316.1
	EGLN3	ENST00000551935.5	TSL:4	n.298-47283C>A		intron	N/A

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

African (AFR) AF: 0.779 AC: 32186 AN: 41338

American (AMR) AF: 0.928 AC: 14159 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 3221 AN: 3468

East Asian (EAS) AF: 0.873 AC: 4492 AN: 5146

South Asian (SAS) AF: 0.885 AC: 4235 AN: 4786

European-Finnish (FIN) AF: 0.901 AC: 9481 AN: 10526

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.898 AC: 60986 AN: 67940

Other (OTH) AF: 0.889 AC: 1866 AN: 2098

Alfa AF: 0.894 Hom.: 97148

Bravo AF: 0.864

Asia WGS AF: 0.865 AC: 3006 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	0.28
DANN	Benign	0.21
PhyloP100		0.0

Splicing

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

Other links and lift over

dbSNP: rs1680730; hg19: chr14-34503651;