rs736801

Positions:

• chr5-132497907-C-T

Variant summary

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

The ENST00000680796.1(IRF1):​c.-5-8424G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,104 control chromosomes in the GnomAD database, including 6,155 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 (6155 hom., cov: 32)
• Consequence: IRF1 ENST00000680796.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400

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=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF1	ENST00000680796.1	c.-5-8424G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38369 AN: 151986 Hom.: 6153 Cov.: 32

Gnomad AFR AF: 0.0908

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.252 AC: 38379 AN: 152104 Hom.: 6155 Cov.: 32 AF XY: 0.242 AC XY: 17986 AN XY: 74384

Gnomad4 AFR AF: 0.0907

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.308

Alfa AF: 0.280 Hom.: 1265

Bravo AF: 0.252

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs736801; hg19: chr5-131833599; COSMIC: COSV60199099;