5-132484285-C-T

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+77G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,517,494 control chromosomes in the GnomAD database, including 85,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11085 hom., cov: 31)
  • Exomes 𝑓: 0.33 (74633 hom.)
• Consequence: IRF1 NM_002198.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.183

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=-0.79).
• BP6: Variant 5-132484285-C-T is Benign according to our data. Variant chr5-132484285-C-T is described in ClinVar as [Benign]. Clinvar id is 2688399.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+77G>A		intron_variant		ENST00000245414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF1	ENST00000245414.9	c.853+77G>A		intron_variant		1	NM_002198.3	P1
IRF1-AS1	ENST00000612967.2	n.281-1907C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 56982 AN: 151372 Hom.: 11071 Cov.: 31

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.327 AC: 447316 AN: 1366004 Hom.: 74633 Cov.: 23 AF XY: 0.329 AC XY: 222980 AN XY: 678514

Gnomad4 AFR exome AF: 0.478

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.328

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.320

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.377 AC: 57039 AN: 151490 Hom.: 11085 Cov.: 31 AF XY: 0.375 AC XY: 27764 AN XY: 73982

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.359

Alfa AF: 0.362 Hom.: 1243

Bravo AF: 0.381

Asia WGS AF: 0.376 AC: 1306 AN: 3476

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	-0.79
Cadd	Benign	3.6
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2070728; hg19: chr5-131819977; COSMIC: COSV55376084; COSMIC: COSV55376084;