rs2070724

Variant summary

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

The NM_002198.3(IRF1):c.545-7T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,610,364 control chromosomes in the GnomAD database, including 97,385 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11305 hom., cov: 33)

Exomes 𝑓: 0.34 ( 86080 hom. )

Consequence

IRF1
NM_002198.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001620

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.132

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=-0.86).

BP6

Variant 5-132486380-A-G is Benign according to our data. Variant chr5-132486380-A-G is described in ClinVar as [Benign]. Clinvar id is 2688381.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	UniProt
IRF1	NM_002198.3 linkuse as main transcript	c.545-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000245414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF1	ENST00000245414.9 linkuse as main transcript	c.545-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002198.3	P1
IRF1-AS1	ENST00000612967.2 linkuse as main transcript	n.469A>G		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57575

AN:

151940

Hom.:

11291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.361

GnomAD3 exomes

AF:

0.348

AC:

86678

AN:

248886

Hom.:

15309

AF XY:

0.348

AC XY:

46862

AN XY:

134780

show subpopulations

Gnomad AFR exome

AF:

0.486

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.317

Gnomad EAS exome

AF:

0.345

Gnomad SAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.325

Gnomad NFE exome

AF:

0.330

Gnomad OTH exome

AF:

0.357

GnomAD4 exome

AF:

0.341

AC:

497694

AN:

1458306

Hom.:

86080

Cov.:

AF XY:

0.342

AC XY:

248129

AN XY:

725544

show subpopulations

Gnomad4 AFR exome

AF:

0.491

Gnomad4 AMR exome

AF:

0.331

Gnomad4 ASJ exome

AF:

0.316

Gnomad4 EAS exome

AF:

0.331

Gnomad4 SAS exome

AF:

0.387

Gnomad4 FIN exome

AF:

0.327

Gnomad4 NFE exome

AF:

0.335

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.379

AC:

57632

AN:

152058

Hom.:

11305

Cov.:

AF XY:

0.378

AC XY:

28112

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.487

Gnomad4 AMR

AF:

0.343

Gnomad4 ASJ

AF:

0.323

Gnomad4 EAS

AF:

0.361

Gnomad4 SAS

AF:

0.410

Gnomad4 FIN

AF:

0.329

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.346

Hom.:

2696

Bravo

AF:

0.382

Asia WGS

AF:

0.377

AC:

1312

AN:

3478

EpiCase

AF:

0.329

EpiControl

AF:

0.325

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

-0.86

Cadd

Benign

5.7

Dann

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0

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