Variant 5-132485554-G-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.717+113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 862,520 control chromosomes in the GnomAD database, including 53,312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11272 hom., cov: 33)

Exomes 𝑓: 0.34 ( 42040 hom. )

Consequence

IRF1
NM_002198.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.558

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=-0.77).

BP6

Variant 5-132485554-G-A is Benign according to our data. Variant chr5-132485554-G-A is described in ClinVar as [Benign]. Clinvar id is 2688410.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 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.717+113C>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.717+113C>T		intron_variant		1	NM_002198.3	ENSP00000245414	P1
IRF1-AS1	ENST00000612967.2 linkuse as main transcript	n.281-638G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57487

AN:

152040

Hom.:

11258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.330

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.359

GnomAD4 exome

AF:

0.341

AC:

241961

AN:

710362

Hom.:

42040

Cov.:

AF XY:

0.342

AC XY:

127702

AN XY:

373270

show subpopulations

Gnomad4 AFR exome

AF:

0.491

Gnomad4 AMR exome

AF:

0.331

Gnomad4 ASJ exome

AF:

0.312

Gnomad4 EAS exome

AF:

0.329

Gnomad4 SAS exome

AF:

0.385

Gnomad4 FIN exome

AF:

0.329

Gnomad4 NFE exome

AF:

0.330

Gnomad4 OTH exome

AF:

0.351

GnomAD4 genome

AF:

0.378

AC:

57544

AN:

152158

Hom.:

11272

Cov.:

AF XY:

0.377

AC XY:

28081

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.487

Gnomad4 AMR

AF:

0.343

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.361

Gnomad4 SAS

AF:

0.410

Gnomad4 FIN

AF:

0.330

Gnomad4 NFE

AF:

0.332

Gnomad4 OTH

AF:

0.359

Alfa

AF:

0.360

Hom.:

1568

Bravo

AF:

0.381

Asia WGS

AF:

0.376

AC:

1310

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 52% of patients studied by a panel of primary immunodeficiencies. Number of patients: 46. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.2

DANN

Benign

0.78

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