5-132482939-G-T

Variant names:

• chr5-132482939-G-T
• rs6873426
• NM_002198.3:c.*1012C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002198.3(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 NM_002198.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• Publications: 13 publications found

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:):

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002198.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF1	NM_002198.3	MANE Select	c.*1012C>A		3_prime_UTR	Exon 10 of 10	NP_002189.1	P10914
	IRF1	NM_001354924.1		c.*1012C>A		3_prime_UTR	Exon 9 of 9	NP_001341853.1	X5D3F6
	IRF1	NM_001354925.1		c.*1012C>A		3_prime_UTR	Exon 8 of 8	NP_001341854.1	A0A7P0TAL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF1	ENST00000245414.9	TSL:1 MANE Select	c.*1012C>A		3_prime_UTR	Exon 10 of 10	ENSP00000245414.4	P10914
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-169+33250G>T		intron	N/A	ENSP00000492349.2	A0A1W2PQ90
	CARINH	ENST00000612967.2	TSL:1	n.281-3253G>T		intron	N/A

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.470 AC: 63 AN: 134

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 2 AN: 6

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.486 AC: 20063 AN: 41290

American (AMR) AF: 0.342 AC: 5215 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1102 AN: 3466

East Asian (EAS) AF: 0.359 AC: 1852 AN: 5162

South Asian (SAS) AF: 0.409 AC: 1967 AN: 4810

European-Finnish (FIN) AF: 0.329 AC: 3458 AN: 10522

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.331 AC: 22497 AN: 67906

Other (OTH) AF: 0.359 AC: 760 AN: 2116

Alfa AF: 0.367 Hom.: 1339

Bravo AF: 0.381

Asia WGS AF: 0.376 AC: 1309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.30
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6873426; hg19: chr5-131818631;