rs11242115

Positions:

• chr5-132490721-G-C

Variant summary

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

The NM_002198.3(IRF1):​c.-182C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,228 control chromosomes in the GnomAD database, including 6,169 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 (6164 hom., cov: 33)
  • Exomes 𝑓: 0.30 (5 hom.)
• Consequence: IRF1 NM_002198.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• 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	UniProt
IRF1	NM_002198.3	c.-182C>G		5_prime_UTR_variant	1/10	ENST00000245414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF1	ENST00000245414.9	c.-182C>G		5_prime_UTR_variant	1/10	1	NM_002198.3	P1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38423 AN: 151990 Hom.: 6162 Cov.: 33

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.00987

Gnomad SAS AF: 0.0963

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.303 AC: 37 AN: 122 Hom.: 5 Cov.: 0 AF XY: 0.261 AC XY: 24 AN XY: 92

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.318

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.253 AC: 38431 AN: 152106 Hom.: 6164 Cov.: 33 AF XY: 0.242 AC XY: 18002 AN XY: 74362

Gnomad4 AFR AF: 0.0915

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.00990

Gnomad4 SAS AF: 0.0964

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.308

Alfa AF: 0.290 Hom.: 951

Bravo AF: 0.252

Asia WGS AF: 0.0820 AC: 285 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	9.0
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs11242115; hg19: chr5-131826413;