rs2522056

Variant names:

• chr5-132466034-G-A
• rs2522056
• ENST00000638452.2:c.-169+16345G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-132466034-G-A
• chr5-132466034-G-C

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-169+16345G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,078 control chromosomes in the GnomAD database, including 4,930 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 0.25 (4930 hom., cov: 33)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 42 publications found

Genes affected

ENSG00000283782 (HGNC:):

CARINH (HGNC:33838): (colitis associated IRF1 antisense regulator of intestinal homeostasis)

IRF1 (HGNC:6116): (interferon regulatory factor 1) The protein encoded by this gene is a transcriptional regulator and tumor suppressor, serving as an activator of genes involved in both innate and acquired immune responses. The encoded protein activates the transcription of genes involved in the body's response to viruses and bacteria, playing a role in cell proliferation, apoptosis, the immune response, and DNA damage response. This protein represses the transcription of several other genes. As a tumor suppressor, it both suppresses tumor cell growth and stimulates an immune response against tumor cells. Defects in this gene have been associated with gastric cancer, myelogenous leukemia, and lung cancer. [provided by RefSeq, Aug 2017]

IRF1 Gene-Disease associations (from GenCC):

• immunodeficiency 117

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARINH	NR_161242.1	n.272-9633G>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000638452.2	c.-169+16345G>A		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37682 AN: 151960 Hom.: 4933 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.248 AC: 37703 AN: 152078 Hom.: 4930 Cov.: 33 AF XY: 0.252 AC XY: 18767 AN XY: 74346

African (AFR) AF: 0.303 AC: 12561 AN: 41462

American (AMR) AF: 0.208 AC: 3180 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3468

East Asian (EAS) AF: 0.398 AC: 2053 AN: 5164

South Asian (SAS) AF: 0.378 AC: 1824 AN: 4822

European-Finnish (FIN) AF: 0.219 AC: 2317 AN: 10568

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14155 AN: 67990

Other (OTH) AF: 0.247 AC: 523 AN: 2116

Alfa AF: 0.224 Hom.: 12321

Bravo AF: 0.247

Asia WGS AF: 0.375 AC: 1303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.7
DANN	Benign	0.50
PhyloP100		-0.091

Splicing

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

Other links and lift over

dbSNP: rs2522056; hg19: chr5-131801726;