rs2706391

Positions:

• chr5-132507614-T-C

Variant summary

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

The ENST00000680796.1(IRF1):​c.-6+1076A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,914 control chromosomes in the GnomAD database, including 2,032 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 0.15 (2032 hom., cov: 31)
• Consequence: IRF1 ENST00000680796.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000680796.1	c.-6+1076A>G		intron_variant				ENSP00000506572

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22501 AN: 151794 Hom.: 2030 Cov.: 31

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.149

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.148 AC: 22507 AN: 151914 Hom.: 2032 Cov.: 31 AF XY: 0.151 AC XY: 11185 AN XY: 74252

Gnomad4 AFR AF: 0.0556

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.147

Alfa AF: 0.167 Hom.: 375

Bravo AF: 0.132

Asia WGS AF: 0.166 AC: 577 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2706391; hg19: chr5-131843306;