rs4531650

Variant names:

• chr14-34047374-C-G
• rs4531650
• ENST00000487915.6:c.3+44947G>C

Variant summary

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

The ENST00000487915.6(EGLN3):​c.3+44947G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,966 control chromosomes in the GnomAD database, including 3,066 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 0.19 (3066 hom., cov: 30)
• Consequence: EGLN3 ENST00000487915.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• Publications: 4 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]

EGLN3-AS1 (HGNC:49077): (EGLN3 antisense RNA 1)

LOC102724945 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGLN3-AS1	NR_184209.1	n.255+6105C>G		intron_variant	Intron 2 of 2
LOC102724945	XR_001750942.2	n.483+44947G>C		intron_variant	Intron 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000487915.6	c.3+44947G>C		intron_variant	Intron 4 of 5	5		ENSP00000451316.1
EGLN3	ENST00000551935.5	n.297+44947G>C		intron_variant	Intron 3 of 4	4
EGLN3-AS1	ENST00000555922.1	n.139+6105C>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28298 AN: 151848 Hom.: 3056 Cov.: 30

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.186 AC: 28334 AN: 151966 Hom.: 3066 Cov.: 30 AF XY: 0.193 AC XY: 14320 AN XY: 74264

African (AFR) AF: 0.196 AC: 8128 AN: 41428

American (AMR) AF: 0.315 AC: 4811 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3470

East Asian (EAS) AF: 0.354 AC: 1822 AN: 5150

South Asian (SAS) AF: 0.245 AC: 1178 AN: 4800

European-Finnish (FIN) AF: 0.143 AC: 1513 AN: 10574

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9656 AN: 67970

Other (OTH) AF: 0.178 AC: 374 AN: 2104

Alfa AF: 0.158 Hom.: 243

Bravo AF: 0.202

Asia WGS AF: 0.292 AC: 1014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.70
PhyloP100		-0.34

Splicing

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

Other links and lift over

dbSNP: rs4531650; hg19: chr14-34516580;