rs2070727

Variant names:

• chr5-132484583-C-A
• rs2070727
• NM_002198.3:c.718-86G>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.718-86G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,548,172 control chromosomes in the GnomAD database, including 93,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11259 hom., cov: 33)
  • Exomes 𝑓: 0.34 (82148 hom.)
• Consequence: IRF1 NM_002198.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0710
• Publications: 25 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=-0.8).
• BP6: Variant 5-132484583-C-A is Benign according to our data. Variant chr5-132484583-C-A is described in ClinVar as Benign. ClinVar VariationId is 2688403.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 rank	MANE	Protein	UniProt
IRF1	NM_002198.3	c.718-86G>T		intron_variant	Intron 8 of 9	ENST00000245414.9	NP_002189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9	c.718-86G>T		intron_variant	Intron 8 of 9	1	NM_002198.3	ENSP00000245414.4
ENSG00000283782	ENST00000638452.2	c.-169+34894C>A		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57459 AN: 152036 Hom.: 11245 Cov.: 33

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.341 AC: 476413 AN: 1396018 Hom.: 82148 Cov.: 22 AF XY: 0.342 AC XY: 237475 AN XY: 694242

African (AFR) AF: 0.493 AC: 15853 AN: 32178

American (AMR) AF: 0.332 AC: 14188 AN: 42796

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 7463 AN: 23920

East Asian (EAS) AF: 0.331 AC: 12990 AN: 39250

South Asian (SAS) AF: 0.388 AC: 31504 AN: 81208

European-Finnish (FIN) AF: 0.330 AC: 16766 AN: 50820

Middle Eastern (MID) AF: 0.389 AC: 1694 AN: 4358

European-Non Finnish (NFE) AF: 0.334 AC: 355713 AN: 1063614

Other (OTH) AF: 0.350 AC: 20242 AN: 57874

GnomAD4 genome AF: 0.378 AC: 57516 AN: 152154 Hom.: 11259 Cov.: 33 AF XY: 0.377 AC XY: 28051 AN XY: 74364

African (AFR) AF: 0.486 AC: 20189 AN: 41500

American (AMR) AF: 0.342 AC: 5239 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1105 AN: 3472

East Asian (EAS) AF: 0.361 AC: 1865 AN: 5168

South Asian (SAS) AF: 0.410 AC: 1980 AN: 4830

European-Finnish (FIN) AF: 0.329 AC: 3473 AN: 10570

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22554 AN: 67996

Other (OTH) AF: 0.360 AC: 760 AN: 2114

Alfa AF: 0.347 Hom.: 4808

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

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 57% of patients studied by a panel of primary immunodeficiencies. Number of patients: 50. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.60
PhyloP100		-0.071
PromoterAI		-0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2070727; hg19: chr5-131820275; COSMIC: COSV55378572; COSMIC: COSV55378572;