5-132485305-G-A

Position:

• chr5-132485305-G-A

Variant summary

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

The NM_002198.3(IRF1):​c.717+362C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 223,062 control chromosomes in the GnomAD database, including 10,258 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 0.25 (6142 hom., cov: 34)
  • Exomes 𝑓: 0.31 (4116 hom.)
• Consequence: IRF1 NM_002198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF1	NM_002198.3	c.717+362C>T		intron_variant		ENST00000245414.9	NP_002189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9	c.717+362C>T		intron_variant		1	NM_002198.3	ENSP00000245414	P1
IRF1-AS1	ENST00000612967.2	n.281-887G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38200 AN: 152098 Hom.: 6142 Cov.: 34

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0854

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.305

GnomAD4 exome AF: 0.307 AC: 21759 AN: 70846 Hom.: 4116 Cov.: 0 AF XY: 0.301 AC XY: 11171 AN XY: 37068

Gnomad4 AFR exome AF: 0.0947

Gnomad4 AMR exome AF: 0.245

Gnomad4 ASJ exome AF: 0.322

Gnomad4 EAS exome AF: 0.000941

Gnomad4 SAS exome AF: 0.0944

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.311

GnomAD4 genome AF: 0.251 AC: 38192 AN: 152216 Hom.: 6142 Cov.: 34 AF XY: 0.240 AC XY: 17876 AN XY: 74406

Gnomad4 AFR AF: 0.0886

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.0854

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.301

Alfa AF: 0.337 Hom.: 8687

Bravo AF: 0.251

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.64

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: rs17622656; hg19: chr5-131820997; COSMIC: COSV55376693; COSMIC: COSV55376693;