5-132482939-G-T

Position:

• chr5-132482939-G-T

Variant summary

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

The ENST00000245414.9(IRF1):​c.*1012C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,718 control chromosomes in the GnomAD database, including 11,150 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 (11150 hom., cov: 30)
  • Exomes 𝑓: 0.46 (11 hom.)
  • Failed GnomAD Quality Control
• Consequence: IRF1 ENST00000245414.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF1	NM_002198.3	c.*1012C>A		3_prime_UTR_variant	10/10	ENST00000245414.9	NP_002189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9	c.*1012C>A		3_prime_UTR_variant	10/10	1	NM_002198.3	ENSP00000245414	P1
IRF1-AS1	ENST00000612967.2	n.281-3253G>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57203 AN: 151598 Hom.: 11135 Cov.: 30

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.359

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.465 AC: 66 AN: 142 Hom.: 11 Cov.: 0 AF XY: 0.476 AC XY: 39 AN XY: 82

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.470

Gnomad4 NFE exome AF: 0.333

GnomAD4 genome AF: 0.377 AC: 57262 AN: 151718 Hom.: 11150 Cov.: 30 AF XY: 0.376 AC XY: 27908 AN XY: 74130

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.359

Alfa AF: 0.362 Hom.: 1239

Bravo AF: 0.381

Asia WGS AF: 0.376 AC: 1309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.30

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: rs6873426; hg19: chr5-131818631;