rs10213701

Positions:

• chr5-132488372-T-A
• chr5-132488372-T-C
• chr5-132488372-T-G

Variant summary

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

The NM_002198.3(IRF1):​c.88-347A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 234,510 control chromosomes in the GnomAD database, including 12,909 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 0.34 (8742 hom., cov: 32)
  • Exomes 𝑓: 0.31 (4167 hom.)
• Consequence: IRF1 NM_002198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

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-AS1 (HGNC:33838): (colitis associated IRF1 antisense regulator of intestinal homeostasis)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF1	NM_002198.3	c.88-347A>T		intron_variant		ENST00000245414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF1	ENST00000245414.9	c.88-347A>T		intron_variant		1	NM_002198.3	P1
IRF1-AS1	ENST00000612967.2	n.2461T>A		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51475 AN: 151920 Hom.: 8738 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.308 AC: 25375 AN: 82472 Hom.: 4167 Cov.: 0 AF XY: 0.312 AC XY: 13907 AN XY: 44576

Gnomad4 AFR exome AF: 0.315

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.310

Gnomad4 EAS exome AF: 0.308

Gnomad4 SAS exome AF: 0.343

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.312

GnomAD4 genome AF: 0.339 AC: 51512 AN: 152038 Hom.: 8742 Cov.: 32 AF XY: 0.340 AC XY: 25233 AN XY: 74322

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.333

Alfa AF: 0.210 Hom.: 434

Bravo AF: 0.336

Asia WGS AF: 0.367 AC: 1279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.5
DANN	Benign	0.82

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: rs10213701; hg19: chr5-131824064;