rs2814993

Variant names:

• chr6-34651116-G-A
• rs2814993
• NM_024294.4:c.313+3509C>T

Variant summary

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

The NM_024294.4(ILRUN):​c.313+3509C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,000 control chromosomes in the GnomAD database, including 2,276 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 0.17 (2276 hom., cov: 31)
• Consequence: ILRUN NM_024294.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630
• Publications: 72 publications found

Genes affected

ILRUN (HGNC:21215): (inflammation and lipid regulator with UBA-like and NBR1-like domains) This gene encodes a protein with N-terminal ubiquitin-associated (UBA)-like and central neighbor of BRCA1 gene 1 (NBR1)-like domains. The protein acts an inhibitor of antiviral and proinflammatory cytokine transcription and as a regulator of the renin-angiotensin-aldosterone system (RAAS). [provided by RefSeq, Jul 2021]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILRUN	NM_024294.4	c.313+3509C>T		intron_variant	Intron 2 of 4	ENST00000374023.8	NP_077270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ILRUN	ENST00000374023.8	c.313+3509C>T		intron_variant	Intron 2 of 4	1	NM_024294.4	ENSP00000363135.3
ILRUN	ENST00000374026.7	c.313+3509C>T		intron_variant	Intron 2 of 3	2		ENSP00000363138.3
ILRUN	ENST00000374021.1	c.91+3509C>T		intron_variant	Intron 2 of 4	3		ENSP00000363133.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25122 AN: 151882 Hom.: 2273 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.165 AC: 25143 AN: 152000 Hom.: 2276 Cov.: 31 AF XY: 0.166 AC XY: 12364 AN XY: 74274

African (AFR) AF: 0.225 AC: 9312 AN: 41444

American (AMR) AF: 0.123 AC: 1876 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3468

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5180

South Asian (SAS) AF: 0.0801 AC: 386 AN: 4818

European-Finnish (FIN) AF: 0.216 AC: 2277 AN: 10554

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10121 AN: 67970

Other (OTH) AF: 0.156 AC: 328 AN: 2108

Alfa AF: 0.146 Hom.: 7375

Bravo AF: 0.162

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.45
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2814993; hg19: chr6-34618893;