5-132484278-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002198.3(IRF1):c.853+84A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,517,182 control chromosomes in the GnomAD database, including 86,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11049 hom., cov: 31)
  • Exomes 𝑓: 0.33 (75719 hom.)
• Consequence: IRF1 NM_002198.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0240

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]

IRF1-AS1 (HGNC:33838): (colitis associated IRF1 antisense regulator of intestinal homeostasis)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-132484278-T-C is Benign according to our data. Variant chr5-132484278-T-C is described in ClinVar as [Benign]. Clinvar id is 2688398.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF1	NM_002198.3	c.853+84A>G		intron_variant		ENST00000245414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF1	ENST00000245414.9	c.853+84A>G		intron_variant		1	NM_002198.3	P1
IRF1-AS1	ENST00000612967.2	n.281-1914T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 56928 AN: 151302 Hom.: 11036 Cov.: 31

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.358

GnomAD4 exome AF: 0.331 AC: 451736 AN: 1365760 Hom.: 75719 Cov.: 23 AF XY: 0.332 AC XY: 224842 AN XY: 677758

Gnomad4 AFR exome AF: 0.481

Gnomad4 AMR exome AF: 0.320

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.329

Gnomad4 SAS exome AF: 0.378

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.376 AC: 56985 AN: 151422 Hom.: 11049 Cov.: 31 AF XY: 0.375 AC XY: 27756 AN XY: 73976

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.358

Alfa AF: 0.157 Hom.: 270

Bravo AF: 0.381

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 58% of patients studied by a panel of primary immunodeficiencies. Number of patients: 51. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.6
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs7701588; hg19: chr5-131819970; COSMIC: COSV55376076; COSMIC: COSV55376076;