rs4531650

Positions:

• chr14-34047374-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_184209.1(EGLN3-AS1):​n.255+6105C>G variant causes a intron, non coding transcript 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-AS1 NR_184209.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337

Genes affected

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

LOC102724945 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
EGLN3-AS1	NR_184209.1	n.255+6105C>G		intron_variant, non_coding_transcript_variant
LOC102724945	XR_001750942.2	n.483+44947G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGLN3-AS1	ENST00000555922.1	n.139+6105C>G		intron_variant, non_coding_transcript_variant		3
EGLN3	ENST00000487915.6	c.3+44947G>C		intron_variant		5
EGLN3	ENST00000551935.5	n.297+44947G>C		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.178

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4531650; hg19: chr14-34516580;