5-132473613-T-C

Variant names:

• chr5-132473613-T-C
• rs2057656
• ENST00000638452.2:c.-169+23924T>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+23924T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 152,006 control chromosomes in the GnomAD database, including 39,506 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 0.72 (39506 hom., cov: 30)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.37
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 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.272-2054T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-169+23924T>C		intron	N/A	ENSP00000492349.2	A0A1W2PQ90
	CARINH	ENST00000612967.2	TSL:1	n.281-12579T>C		intron	N/A
	ENSG00000283782	ENST00000638568.2	TSL:5	c.-311+23924T>C		intron	N/A	ENSP00000491158.2	A0A1W2PQ90

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108969 AN: 151888 Hom.: 39469 Cov.: 30

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.717 AC: 109052 AN: 152006 Hom.: 39506 Cov.: 30 AF XY: 0.708 AC XY: 52609 AN XY: 74292

African (AFR) AF: 0.745 AC: 30859 AN: 41430

American (AMR) AF: 0.623 AC: 9527 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2958 AN: 3470

East Asian (EAS) AF: 0.661 AC: 3408 AN: 5158

South Asian (SAS) AF: 0.590 AC: 2840 AN: 4816

European-Finnish (FIN) AF: 0.632 AC: 6677 AN: 10572

Middle Eastern (MID) AF: 0.791 AC: 231 AN: 292

European-Non Finnish (NFE) AF: 0.738 AC: 50188 AN: 67974

Other (OTH) AF: 0.761 AC: 1601 AN: 2104

Alfa AF: 0.630 Hom.: 1967

Bravo AF: 0.720

Asia WGS AF: 0.633 AC: 2203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0030
DANN	Benign	0.60
PhyloP100		-3.4

Splicing

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

Other links and lift over

dbSNP: rs2057656; hg19: chr5-131809305;