5-132484108-G-A

Variant names:

• chr5-132484108-G-A
• rs2070730
• NM_002198.3:c.854-33C>T

Variant summary

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

The NM_002198.3(IRF1):​c.854-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,607,370 control chromosomes in the GnomAD database, including 96,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11107 hom., cov: 31)
  • Exomes 𝑓: 0.34 (85204 hom.)
• Consequence: IRF1 NM_002198.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.362
• Publications: 16 publications found

Genes affected

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]

ENSG00000283782 (HGNC:):

CARINH (HGNC:33838): (colitis associated IRF1 antisense regulator of intestinal homeostasis)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-132484108-G-A is Benign according to our data. Variant chr5-132484108-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688379.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002198.3. 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
	IRF1	NM_002198.3	MANE Select	c.854-33C>T		intron	N/A	NP_002189.1
	IRF1	NM_001354924.1		c.731-33C>T		intron	N/A	NP_001341853.1
	IRF1	NM_001354925.1		c.668-33C>T		intron	N/A	NP_001341854.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF1	ENST00000245414.9	TSL:1 MANE Select	c.854-33C>T		intron	N/A	ENSP00000245414.4
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-169+34419G>A		intron	N/A	ENSP00000492349.2
	CARINH	ENST00000612967.2	TSL:1	n.281-2084G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57105 AN: 151544 Hom.: 11093 Cov.: 31

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.358

GnomAD2 exomes AF: 0.347 AC: 86691 AN: 249788 AF XY: 0.346

Gnomad AFR exome AF: 0.486

Gnomad AMR exome AF: 0.326

Gnomad ASJ exome AF: 0.313

Gnomad EAS exome AF: 0.344

Gnomad FIN exome AF: 0.326

Gnomad NFE exome AF: 0.329

Gnomad OTH exome AF: 0.354

GnomAD4 exome AF: 0.340 AC: 494527 AN: 1455708 Hom.: 85204 Cov.: 33 AF XY: 0.341 AC XY: 246456 AN XY: 723688

African (AFR) AF: 0.491 AC: 16384 AN: 33362

American (AMR) AF: 0.331 AC: 14757 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 8104 AN: 25994

East Asian (EAS) AF: 0.331 AC: 13077 AN: 39560

South Asian (SAS) AF: 0.387 AC: 33280 AN: 86016

European-Finnish (FIN) AF: 0.329 AC: 17525 AN: 53282

Middle Eastern (MID) AF: 0.400 AC: 2231 AN: 5572

European-Non Finnish (NFE) AF: 0.333 AC: 368257 AN: 1107184

Other (OTH) AF: 0.348 AC: 20912 AN: 60130

GnomAD4 genome AF: 0.377 AC: 57162 AN: 151662 Hom.: 11107 Cov.: 31 AF XY: 0.376 AC XY: 27856 AN XY: 74106

African (AFR) AF: 0.485 AC: 20037 AN: 41296

American (AMR) AF: 0.342 AC: 5219 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1106 AN: 3468

East Asian (EAS) AF: 0.359 AC: 1851 AN: 5158

South Asian (SAS) AF: 0.410 AC: 1973 AN: 4816

European-Finnish (FIN) AF: 0.326 AC: 3419 AN: 10494

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22454 AN: 67862

Other (OTH) AF: 0.358 AC: 752 AN: 2100

Alfa AF: 0.348 Hom.: 3344

Bravo AF: 0.381

Asia WGS AF: 0.376 AC: 1308 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.43
PhyloP100		-0.36
PromoterAI		-0.026	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: rs2070730; hg19: chr5-131819800; COSMIC: COSV55378267; COSMIC: COSV55378267;