rs1471639

Variant names:

• chr14-34013320-A-C
• rs1471639
• ENST00000487915.6:c.3+79001T>G

Your query was ambiguous. Multiple possible variants found:

• chr14-34013320-A-C
• chr14-34013320-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000487915.6(EGLN3):​c.3+79001T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 152,180 control chromosomes in the GnomAD database, including 12 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 0.0056 (12 hom., cov: 32)
• Consequence: EGLN3 ENST00000487915.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425
• 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=-0.85).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00561 (853/152180) while in subpopulation AFR AF = 0.0195 (809/41502). AF 95% confidence interval is 0.0184. There are 12 homozygotes in GnomAd4. There are 368 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC102724945	XR_001750942.2	n.484-26158T>G		intron_variant	Intron 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000487915.6	c.3+79001T>G		intron_variant	Intron 4 of 5	5		ENSP00000451316.1
EGLN3	ENST00000550114.5	n.55+5281T>G		intron_variant	Intron 1 of 2	4
EGLN3	ENST00000551935.5	n.298-26158T>G		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.00558 AC: 849 AN: 152062 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00382

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

GnomAD4 genome AF: 0.00561 AC: 853 AN: 152180 Hom.: 12 Cov.: 32 AF XY: 0.00495 AC XY: 368 AN XY: 74398

African (AFR) AF: 0.0195 AC: 809 AN: 41502

American (AMR) AF: 0.00190 AC: 29 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68002

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00 Hom.: 634

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.64
PhyloP100		-0.42

Splicing

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

Other links and lift over

dbSNP: rs1471639; hg19: chr14-34482526;