rs2070729

Variant names:

• chr5-132484229-C-A
• rs2070729
• NM_002198.3:c.853+133G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-132484229-C-A
• chr5-132484229-C-G
• chr5-132484229-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002198.3(IRF1):​c.853+133G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,411,578 control chromosomes in the GnomAD database, including 158,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (21002 hom., cov: 31)
  • Exomes 𝑓: 0.46 (137670 hom.)
• Consequence: IRF1 NM_002198.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.677
• Publications: 69 publications found

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]

ENSG00000283782 (HGNC:):

CARINH (HGNC:33838): (colitis associated IRF1 antisense regulator of intestinal homeostasis)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-132484229-C-A is Benign according to our data. Variant chr5-132484229-C-A is described in ClinVar as Benign. ClinVar VariationId is 2688486.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF1	NM_002198.3	c.853+133G>T		intron_variant	Intron 9 of 9	ENST00000245414.9	NP_002189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9	c.853+133G>T		intron_variant	Intron 9 of 9	1	NM_002198.3	ENSP00000245414.4
ENSG00000283782	ENST00000638452.2	c.-169+34540C>A		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78525 AN: 151730 Hom.: 20968 Cov.: 31

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.487

GnomAD4 exome AF: 0.461 AC: 580318 AN: 1259730 Hom.: 137670 Cov.: 18 AF XY: 0.464 AC XY: 290259 AN XY: 625902

African (AFR) AF: 0.618 AC: 17780 AN: 28786

American (AMR) AF: 0.608 AC: 22619 AN: 37200

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 8382 AN: 20958

East Asian (EAS) AF: 0.693 AC: 26585 AN: 38336

South Asian (SAS) AF: 0.600 AC: 43469 AN: 72484

European-Finnish (FIN) AF: 0.499 AC: 24599 AN: 49284

Middle Eastern (MID) AF: 0.538 AC: 2480 AN: 4612

European-Non Finnish (NFE) AF: 0.429 AC: 409311 AN: 955014

Other (OTH) AF: 0.473 AC: 25093 AN: 53056

GnomAD4 genome AF: 0.518 AC: 78617 AN: 151848 Hom.: 21002 Cov.: 31 AF XY: 0.525 AC XY: 38950 AN XY: 74174

African (AFR) AF: 0.621 AC: 25707 AN: 41392

American (AMR) AF: 0.548 AC: 8357 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1431 AN: 3472

East Asian (EAS) AF: 0.699 AC: 3602 AN: 5156

South Asian (SAS) AF: 0.614 AC: 2957 AN: 4814

European-Finnish (FIN) AF: 0.500 AC: 5270 AN: 10542

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29788 AN: 67902

Other (OTH) AF: 0.489 AC: 1028 AN: 2102

Alfa AF: 0.466 Hom.: 52419

Bravo AF: 0.523

Asia WGS AF: 0.615 AC: 2141 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported.

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.82
DANN	Benign	0.60
PhyloP100		-0.68
PromoterAI		-0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs2070729; hg19: chr5-131819921;