rs2070723

Positions:

• chr5-132487495-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002198.3(IRF1):​c.188-365T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 342,484 control chromosomes in the GnomAD database, including 22,692 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (11319 hom., cov: 32)
  • Exomes 𝑓: 0.34 (11373 hom.)
• Consequence: IRF1 NM_002198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF1	NM_002198.3	c.188-365T>C		intron_variant		ENST00000245414.9	NP_002189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9	c.188-365T>C		intron_variant		1	NM_002198.3	ENSP00000245414.4
ENSG00000283782	ENST00000640655.2	c.-169+835A>G		intron_variant		5		ENSP00000491596.2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57591 AN: 151930 Hom.: 11305 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.229

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: 0.494

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.337 AC: 64185 AN: 190436 Hom.: 11373 Cov.: 0 AF XY: 0.339 AC XY: 34465 AN XY: 101550

Gnomad4 AFR exome AF: 0.486

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.310

Gnomad4 EAS exome AF: 0.330

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.339

GnomAD4 genome AF: 0.379 AC: 57648 AN: 152048 Hom.: 11319 Cov.: 32 AF XY: 0.378 AC XY: 28124 AN XY: 74324

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: 0.360

Alfa AF: 0.363 Hom.: 1250

Bravo AF: 0.382

Asia WGS AF: 0.377 AC: 1311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.15

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

Other links and lift over

dbSNP: rs2070723; hg19: chr5-131823187;