5-132474927-C-T

Variant names:

• chr5-132474927-C-T
• rs2706381
• ENST00000638452.2:c.-169+25238C>T

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-169+25238C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,090 control chromosomes in the GnomAD database, including 4,763 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 0.24 (4763 hom., cov: 32)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 18 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARINH	NR_161242.1		n.272-740C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-169+25238C>T		intron	N/A	ENSP00000492349.2
	CARINH	ENST00000612967.2	TSL:1	n.281-11265C>T		intron	N/A
	ENSG00000283782	ENST00000638568.2	TSL:5	c.-311+25238C>T		intron	N/A	ENSP00000491158.2

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37042 AN: 151972 Hom.: 4766 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.244 AC: 37063 AN: 152090 Hom.: 4763 Cov.: 32 AF XY: 0.248 AC XY: 18450 AN XY: 74352

African (AFR) AF: 0.290 AC: 12030 AN: 41474

American (AMR) AF: 0.206 AC: 3151 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 938 AN: 3472

East Asian (EAS) AF: 0.390 AC: 2014 AN: 5164

South Asian (SAS) AF: 0.373 AC: 1798 AN: 4814

European-Finnish (FIN) AF: 0.218 AC: 2311 AN: 10586

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14155 AN: 67978

Other (OTH) AF: 0.245 AC: 519 AN: 2116

Alfa AF: 0.226 Hom.: 1190

Bravo AF: 0.243

Asia WGS AF: 0.370 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.23
DANN	Benign	0.43
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs2706381; hg19: chr5-131810619; COSMIC: COSV66755062; COSMIC: COSV66755062;