rs2070722

Positions:

• chr5-132488794-A-C

Variant summary

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

The NM_002198.3(IRF1):​c.87+598T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 153,290 control chromosomes in the GnomAD database, including 11,359 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 (11308 hom., cov: 32)
  • Exomes 𝑓: 0.27 (51 hom.)
• Consequence: IRF1 NM_002198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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	c.87+598T>G		intron_variant		ENST00000245414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF1	ENST00000245414.9	c.87+598T>G		intron_variant		1	NM_002198.3	P1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57608 AN: 151930 Hom.: 11294 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.269 AC: 334 AN: 1242 Hom.: 51 Cov.: 0 AF XY: 0.279 AC XY: 179 AN XY: 642

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.306

GnomAD4 genome AF: 0.379 AC: 57665 AN: 152048 Hom.: 11308 Cov.: 32 AF XY: 0.378 AC XY: 28123 AN XY: 74306

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.360

Alfa AF: 0.368 Hom.: 2270

Bravo AF: 0.382

Asia WGS AF: 0.377 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.2
DANN	Benign	0.49

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: rs2070722; hg19: chr5-131824486;