5-132444165-T-C

Variant names:

• chr5-132444165-T-C
• rs4540166
• ENST00000638452.2:c.-208-5485T>C

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-208-5485T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,156 control chromosomes in the GnomAD database, including 48,950 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 0.80 (48950 hom., cov: 32)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 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.232-5485T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-208-5485T>C		intron	N/A	ENSP00000492349.2	A0A1W2PQ90
	CARINH	ENST00000612967.2	TSL:1	n.241-5485T>C		intron	N/A
	ENSG00000283782	ENST00000638568.2	TSL:5	c.-350-5485T>C		intron	N/A	ENSP00000491158.2	A0A1W2PQ90

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121557 AN: 152038 Hom.: 48917 Cov.: 32

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.799 AC: 121642 AN: 152156 Hom.: 48950 Cov.: 32 AF XY: 0.795 AC XY: 59104 AN XY: 74382

African (AFR) AF: 0.861 AC: 35756 AN: 41512

American (AMR) AF: 0.792 AC: 12112 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3054 AN: 3472

East Asian (EAS) AF: 0.893 AC: 4628 AN: 5180

South Asian (SAS) AF: 0.676 AC: 3256 AN: 4816

European-Finnish (FIN) AF: 0.688 AC: 7286 AN: 10588

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52799 AN: 67972

Other (OTH) AF: 0.825 AC: 1743 AN: 2114

Alfa AF: 0.789 Hom.: 15046

Bravo AF: 0.815

Asia WGS AF: 0.738 AC: 2564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.59
PhyloP100		-0.066

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: rs4540166; hg19: chr5-131779857;