5-132468176-A-G

Variant names:

• chr5-132468176-A-G
• rs10067603
• ENST00000638452.2:c.-169+18487A>G

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-169+18487A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,080 control chromosomes in the GnomAD database, including 3,099 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 (3098 hom., cov: 30)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• 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=-1.02).
• 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.272-7491A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-169+18487A>G		intron	N/A	ENSP00000492349.2
	CARINH	ENST00000612967.2	TSL:1	n.281-18016A>G		intron	N/A
	Y_RNA	ENST00000365663.1	TSL:6	n.30A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27267 AN: 151936 Hom.: 3095 Cov.: 30

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.154 AC: 4 AN: 26 Hom.: 1 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AF: 0.188 AC: 3 AN: 16

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.179 AC: 27277 AN: 152054 Hom.: 3098 Cov.: 30 AF XY: 0.186 AC XY: 13798 AN XY: 74300

African (AFR) AF: 0.0569 AC: 2361 AN: 41488

American (AMR) AF: 0.207 AC: 3161 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3472

East Asian (EAS) AF: 0.103 AC: 534 AN: 5180

South Asian (SAS) AF: 0.324 AC: 1561 AN: 4818

European-Finnish (FIN) AF: 0.316 AC: 3334 AN: 10538

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

European-Non Finnish (NFE) AF: 0.226 AC: 15387 AN: 67966

Other (OTH) AF: 0.161 AC: 340 AN: 2114

Alfa AF: 0.204 Hom.: 464

Bravo AF: 0.160

Asia WGS AF: 0.230 AC: 800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.38
PhyloP100		-0.10

Splicing

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

Other links and lift over

dbSNP: rs10067603; hg19: chr5-131803868;