chr14-34130140-G-A

Variant names:

• chr14-34130140-G-A
• rs4981220
• ENST00000487915.6:c.-79-37738C>T

Variant summary

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

The ENST00000487915.6(EGLN3):​c.-79-37738C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,022 control chromosomes in the GnomAD database, including 6,190 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 0.28 (6189 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: EGLN3 ENST00000487915.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 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.-79-37738C>T		intron	N/A	ENSP00000451316.1
	EGLN3	ENST00000464521.6	TSL:5	n.178-2996C>T		intron	N/A
	EGLN3	ENST00000546681.5	TSL:5	n.213-2996C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42603 AN: 151886 Hom.: 6176 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.500 AC: 9 AN: 18 Hom.: 1 AF XY: 0.583 AC XY: 7 AN XY: 12

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 7 AN: 14

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.281 AC: 42659 AN: 152004 Hom.: 6189 Cov.: 32 AF XY: 0.285 AC XY: 21154 AN XY: 74272

African (AFR) AF: 0.215 AC: 8930 AN: 41472

American (AMR) AF: 0.345 AC: 5273 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 982 AN: 3466

East Asian (EAS) AF: 0.421 AC: 2170 AN: 5152

South Asian (SAS) AF: 0.280 AC: 1351 AN: 4818

European-Finnish (FIN) AF: 0.330 AC: 3479 AN: 10544

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19447 AN: 67946

Other (OTH) AF: 0.307 AC: 647 AN: 2108

Alfa AF: 0.287 Hom.: 12230

Bravo AF: 0.283

Asia WGS AF: 0.377 AC: 1310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.91
DANN	Benign	0.80
PhyloP100		-0.43

Splicing

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

Other links and lift over

dbSNP: rs4981220; hg19: chr14-34599346;