rs9282763

Variant names:

• chr5-132486441-T-C
• rs9282763
• ENST00000612967.2:n.530T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000612967.2(CARINH):​n.530T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,608,276 control chromosomes in the GnomAD database, including 97,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11331 hom., cov: 33)
  • Exomes 𝑓: 0.34 (85866 hom.)
• Consequence: CARINH ENST00000612967.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.32
• Publications: 20 publications found

Genes affected

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

ENSG00000283782 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-132486441-T-C is Benign according to our data. Variant chr5-132486441-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688382.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF1	NM_002198.3	c.545-68A>G		intron_variant	Intron 6 of 9	ENST00000245414.9	NP_002189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9	c.545-68A>G		intron_variant	Intron 6 of 9	1	NM_002198.3	ENSP00000245414.4
ENSG00000283782	ENST00000638452.2	c.-169+36752T>C		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57648 AN: 152030 Hom.: 11317 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.360

GnomAD2 exomes AF: 0.347 AC: 85735 AN: 246886 AF XY: 0.347

Gnomad AFR exome AF: 0.486

Gnomad AMR exome AF: 0.327

Gnomad ASJ exome AF: 0.317

Gnomad EAS exome AF: 0.345

Gnomad FIN exome AF: 0.322

Gnomad NFE exome AF: 0.329

Gnomad OTH exome AF: 0.356

GnomAD4 exome AF: 0.341 AC: 496764 AN: 1456128 Hom.: 85866 Cov.: 34 AF XY: 0.342 AC XY: 247669 AN XY: 724490

African (AFR) AF: 0.491 AC: 16437 AN: 33452

American (AMR) AF: 0.331 AC: 14765 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 8254 AN: 26132

East Asian (EAS) AF: 0.331 AC: 13116 AN: 39650

South Asian (SAS) AF: 0.387 AC: 33267 AN: 86000

European-Finnish (FIN) AF: 0.325 AC: 16053 AN: 49366

Middle Eastern (MID) AF: 0.404 AC: 2329 AN: 5764

European-Non Finnish (NFE) AF: 0.334 AC: 371475 AN: 1110792

Other (OTH) AF: 0.349 AC: 21068 AN: 60332

GnomAD4 genome AF: 0.379 AC: 57705 AN: 152148 Hom.: 11331 Cov.: 33 AF XY: 0.378 AC XY: 28154 AN XY: 74388

African (AFR) AF: 0.487 AC: 20232 AN: 41508

American (AMR) AF: 0.343 AC: 5246 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3470

East Asian (EAS) AF: 0.361 AC: 1861 AN: 5160

South Asian (SAS) AF: 0.410 AC: 1981 AN: 4830

European-Finnish (FIN) AF: 0.330 AC: 3495 AN: 10596

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.333 AC: 22661 AN: 67986

Other (OTH) AF: 0.360 AC: 759 AN: 2110

Alfa AF: 0.353 Hom.: 2150

Bravo AF: 0.382

Asia WGS AF: 0.377 AC: 1312 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 66% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		-1.3
PromoterAI		-0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs9282763; hg19: chr5-131822133; COSMIC: COSV55376972; COSMIC: COSV55376972;