chr5-132466255-G-C

Variant names:

• chr5-132466255-G-C
• rs2522057
• ENST00000638452.2:c.-169+16566G>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+16566G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,132 control chromosomes in the GnomAD database, including 38,750 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 0.70 (38750 hom., cov: 33)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 40 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000638452.2. 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
	CARINH	NR_161242.1		n.272-9412G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-169+16566G>C		intron	N/A	ENSP00000492349.2	A0A1W2PQ90
	CARINH	ENST00000612967.2	TSL:1	n.280+16566G>C		intron	N/A
	ENSG00000283782	ENST00000638568.2	TSL:5	c.-311+16566G>C		intron	N/A	ENSP00000491158.2	A0A1W2PQ90

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106744 AN: 152014 Hom.: 38701 Cov.: 33

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.702 AC: 106851 AN: 152132 Hom.: 38750 Cov.: 33 AF XY: 0.713 AC XY: 53035 AN XY: 74376

African (AFR) AF: 0.852 AC: 35353 AN: 41508

American (AMR) AF: 0.704 AC: 10768 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2115 AN: 3468

East Asian (EAS) AF: 0.978 AC: 5072 AN: 5188

South Asian (SAS) AF: 0.870 AC: 4195 AN: 4820

European-Finnish (FIN) AF: 0.691 AC: 7306 AN: 10566

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.589 AC: 40065 AN: 67972

Other (OTH) AF: 0.659 AC: 1391 AN: 2110

Alfa AF: 0.545 Hom.: 1501

Bravo AF: 0.705

Asia WGS AF: 0.891 AC: 3098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.25
DANN	Benign	0.54
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs2522057; hg19: chr5-131801947;