Genetic Variant IRF1:c.853+77G>A (chr5-132484285-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

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

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.183

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:

ENSG00000283782 (HGNC:):

ENSG00000283782 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=-0.79).

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 rank	MANE	Protein	UniProt
IRF1	NM_002198.3 link	c.853+77G>A		intron_variant	Intron 9 of 9	ENST00000245414.9	NP_002189.1	P10914Q6FHN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9 link	c.853+77G>A		intron_variant	Intron 9 of 9	1	NM_002198.3	ENSP00000245414.4		P10914
ENSG00000283782	ENST00000640655.2 link	c.-637-1907C>T		intron_variant	Intron 1 of 25	5		ENSP00000491596.2		A0A1W2PQ90

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

56982

AN:

151372

Hom.:

11071

Cov.:

show subpopulations

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.:

AF XY:

0.329

AC XY:

222980

AN XY:

678514

show subpopulations

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.:

AF XY:

0.375

AC XY:

27764

AN XY:

73982

show subpopulations

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

LINK: link

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 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

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