Variant rs2070730 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.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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.362

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=-0.82).

BP6

Variant 5-132484108-G-A is Benign according to our data. Variant chr5-132484108-G-A is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF1	NM_002198.3 linkuse as main transcript	c.854-33C>T		intron_variant		ENST00000245414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF1	ENST00000245414.9 linkuse as main transcript	c.854-33C>T		intron_variant		1	NM_002198.3	P1
IRF1-AS1	ENST00000612967.2 linkuse as main transcript	n.281-2084G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.377

AC:

57105

AN:

151544

Hom.:

11093

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.347

AC:

86691

AN:

249788

Hom.:

15078

AF XY:

0.346

AC XY:

46717

AN XY:

134972

show subpopulations

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 SAS exome

AF:

0.391

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.:

AF XY:

0.341

AC XY:

246456

AN XY:

723688

show subpopulations

Gnomad4 AFR exome

AF:

0.491

Gnomad4 AMR exome

AF:

0.331

Gnomad4 ASJ exome

AF:

0.312

Gnomad4 EAS exome

AF:

0.331

Gnomad4 SAS exome

AF:

0.387

Gnomad4 FIN exome

AF:

0.329

Gnomad4 NFE exome

AF:

0.333

Gnomad4 OTH exome

AF:

0.348

GnomAD4 genome

AF:

0.377

AC:

57162

AN:

151662

Hom.:

11107

Cov.:

AF XY:

0.376

AC XY:

27856

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.485

Gnomad4 AMR

AF:

0.342

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.359

Gnomad4 SAS

AF:

0.410

Gnomad4 FIN

AF:

0.326

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.358

Alfa

AF:

0.347

Hom.:

1674

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

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 66% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.8

DANN

Benign

0.43

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