chr5-132465466-C-T

Variant names:

• chr5-132465466-C-T
• rs10077785
• ENST00000638452.2:c.-169+15777C>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+15777C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,256 control chromosomes in the GnomAD database, including 3,171 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 0.18 (3171 hom., cov: 33)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 27 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 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.272-10201C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-169+15777C>T		intron	N/A	ENSP00000492349.2
	CARINH	ENST00000612967.2	TSL:1	n.280+15777C>T		intron	N/A
	ENSG00000283782	ENST00000638568.2	TSL:5	c.-311+15777C>T		intron	N/A	ENSP00000491158.2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27576 AN: 152138 Hom.: 3168 Cov.: 33

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0951

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.181 AC: 27586 AN: 152256 Hom.: 3171 Cov.: 33 AF XY: 0.187 AC XY: 13907 AN XY: 74444

African (AFR) AF: 0.0578 AC: 2401 AN: 41570

American (AMR) AF: 0.208 AC: 3181 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3470

East Asian (EAS) AF: 0.0951 AC: 494 AN: 5192

South Asian (SAS) AF: 0.324 AC: 1566 AN: 4828

European-Finnish (FIN) AF: 0.317 AC: 3353 AN: 10584

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15637 AN: 67996

Other (OTH) AF: 0.164 AC: 346 AN: 2114

Alfa AF: 0.201 Hom.: 9154

Bravo AF: 0.162

Asia WGS AF: 0.228 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.5
DANN	Benign	0.62
PhyloP100		-0.018

Splicing

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

Other links and lift over

dbSNP: rs10077785; hg19: chr5-131801158;