rs1154103

Variant names:

• chr14-34191874-G-A
• rs1154103
• ENST00000487915.6:c.-236+7613C>T

Variant summary

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

The ENST00000548285.5(EGLN3):​n.119-22228C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0741 in 152,230 control chromosomes in the GnomAD database, including 938 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 0.074 (938 hom., cov: 32)
• Consequence: EGLN3 ENST00000548285.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 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.-236+7613C>T		intron	N/A	ENSP00000451316.1
	EGLN3	ENST00000546681.5	TSL:5	n.57-22228C>T		intron	N/A
	EGLN3	ENST00000548285.5	TSL:3	n.119-22228C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11258 AN: 152112 Hom.: 936 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.0746

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

GnomAD4 genome AF: 0.0741 AC: 11285 AN: 152230 Hom.: 938 Cov.: 32 AF XY: 0.0707 AC XY: 5266 AN XY: 74434

African (AFR) AF: 0.209 AC: 8680 AN: 41488

American (AMR) AF: 0.0545 AC: 833 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0342 AC: 165 AN: 4824

European-Finnish (FIN) AF: 0.00603 AC: 64 AN: 10610

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0192 AC: 1307 AN: 68032

Other (OTH) AF: 0.0738 AC: 156 AN: 2114

Alfa AF: 0.0533 Hom.: 64

Bravo AF: 0.0849

Asia WGS AF: 0.0260 AC: 90 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.81
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs1154103; hg19: chr14-34661080;