rs41525648

Positions:

• chr5-132492083-A-G

Variant summary

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

The ENST00000680796.1(IRF1):​c.-5-2600T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,906 control chromosomes in the GnomAD database, including 17,482 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 0.47 (17482 hom., cov: 32)
• Consequence: IRF1 ENST00000680796.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 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.-5-2600T>C		intron_variant				ENSP00000506572
IRF1	ENST00000681584.1	c.-5-2600T>C		intron_variant				ENSP00000505448

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70819 AN: 151788 Hom.: 17482 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.466 AC: 70837 AN: 151906 Hom.: 17482 Cov.: 32 AF XY: 0.460 AC XY: 34136 AN XY: 74236

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.502

Alfa AF: 0.483 Hom.: 2611

Bravo AF: 0.458

Asia WGS AF: 0.381 AC: 1321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.0
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41525648; hg19: chr5-131827775; COSMIC: COSV55376719; COSMIC: COSV55376719;