Variant 5-132484229-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002198.3(IRF1):c.853+133G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,411,578 control chromosomes in the GnomAD database, including 158,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.52 ( 21002 hom., cov: 31)

Exomes 𝑓: 0.46 ( 137670 hom. )

Consequence

IRF1
NM_002198.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.677

Variant links:

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 links:

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

IRF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 5-132484229-C-A is Benign according to our data. Variant chr5-132484229-C-A is described in ClinVar as [Benign]. Clinvar id is 2688486.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF1	NM_002198.3 linkuse as main transcript	c.853+133G>T		intron_variant		ENST00000245414.9	NP_002189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9 linkuse as main transcript	c.853+133G>T		intron_variant		1	NM_002198.3	ENSP00000245414	P1
IRF1-AS1	ENST00000612967.2 linkuse as main transcript	n.281-1963C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78525

AN:

151730

Hom.:

20968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.621

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.547

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.699

Gnomad SAS

AF:

0.614

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.487

GnomAD4 exome

AF:

0.461

AC:

580318

AN:

1259730

Hom.:

137670

Cov.:

AF XY:

0.464

AC XY:

290259

AN XY:

625902

show subpopulations

Gnomad4 AFR exome

AF:

0.618

Gnomad4 AMR exome

AF:

0.608

Gnomad4 ASJ exome

AF:

0.400

Gnomad4 EAS exome

AF:

0.693

Gnomad4 SAS exome

AF:

0.600

Gnomad4 FIN exome

AF:

0.499

Gnomad4 NFE exome

AF:

0.429

Gnomad4 OTH exome

AF:

0.473

GnomAD4 genome

AF:

0.518

AC:

78617

AN:

151848

Hom.:

21002

Cov.:

AF XY:

0.525

AC XY:

38950

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.621

Gnomad4 AMR

AF:

0.548

Gnomad4 ASJ

AF:

0.412

Gnomad4 EAS

AF:

0.699

Gnomad4 SAS

AF:

0.614

Gnomad4 FIN

AF:

0.500

Gnomad4 NFE

AF:

0.439

Gnomad4 OTH

AF:

0.489

Alfa

AF:

0.459

Hom.:

16429

Bravo

AF:

0.523

Asia WGS

AF:

0.615

AC:

2141

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.82

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over