Variant 5-132487827-A-G 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.187+99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 747,106 control chromosomes in the GnomAD database, including 42,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.34 ( 8934 hom., cov: 32)

Exomes 𝑓: 0.33 ( 33309 hom. )

Consequence

IRF1
NM_002198.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.125

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=-0.81).

BP6

Variant 5-132487827-A-G is Benign according to our data. Variant chr5-132487827-A-G is described in ClinVar as [Benign]. Clinvar id is 2688210.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.394 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.187+99T>C		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.187+99T>C		intron_variant		1	NM_002198.3	ENSP00000245414	P1
IRF1-AS1	ENST00000612967.2 linkuse as main transcript	n.1916A>G		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

51974

AN:

151890

Hom.:

8930

Cov.:

show subpopulations

Gnomad AFR

AF:

0.368

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.325

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.335

GnomAD4 exome

AF:

0.333

AC:

198341

AN:

595098

Hom.:

33309

Cov.:

AF XY:

0.336

AC XY:

106454

AN XY:

317032

show subpopulations

Gnomad4 AFR exome

AF:

0.370

Gnomad4 AMR exome

AF:

0.317

Gnomad4 ASJ exome

AF:

0.316

Gnomad4 EAS exome

AF:

0.330

Gnomad4 SAS exome

AF:

0.382

Gnomad4 FIN exome

AF:

0.323

Gnomad4 NFE exome

AF:

0.326

Gnomad4 OTH exome

AF:

0.337

GnomAD4 genome

AF:

0.342

AC:

52012

AN:

152008

Hom.:

8934

Cov.:

AF XY:

0.343

AC XY:

25468

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.368

Gnomad4 AMR

AF:

0.325

Gnomad4 ASJ

AF:

0.323

Gnomad4 EAS

AF:

0.360

Gnomad4 SAS

AF:

0.409

Gnomad4 FIN

AF:

0.327

Gnomad4 NFE

AF:

0.329

Gnomad4 OTH

AF:

0.335

Alfa

AF:

0.338

Hom.:

1903

Bravo

AF:

0.340

Asia WGS

AF:

0.368

AC:

1282

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 35% of patients studied by a panel of primary immunodeficiencies. Number of patients: 33. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.3

DANN

Benign

0.68

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