5-132484229-C-T

Variant names:

• chr5-132484229-C-T
• rs2070729
• NM_002198.3:c.853+133G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002198.3(IRF1):​c.853+133G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000791 in 1,263,700 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: IRF1 NM_002198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677
• Publications: 70 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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.853+133G>A		intron	N/A	NP_002189.1	P10914
	IRF1	NM_001354924.1		c.730+133G>A		intron	N/A	NP_001341853.1	X5D3F6
	IRF1	NM_001354925.1		c.668-154G>A		intron	N/A	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.853+133G>A		intron	N/A	ENSP00000245414.4	P10914
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-169+34540C>T		intron	N/A	ENSP00000492349.2	A0A1W2PQ90
	CARINH	ENST00000612967.2	TSL:1	n.281-1963C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.91e-7 AC: 1 AN: 1263700 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 627776

African (AFR) AF: 0.00 AC: 0 AN: 28866

American (AMR) AF: 0.00 AC: 0 AN: 37270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20984

East Asian (EAS) AF: 0.00 AC: 0 AN: 38356

South Asian (SAS) AF: 0.00 AC: 0 AN: 72576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4620

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 958532

Other (OTH) AF: 0.00 AC: 0 AN: 53162

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.86
PhyloP100		-0.68
PromoterAI		-0.039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2070729; hg19: chr5-131819921;