5-132474927-C-T

Position:

• chr5-132474927-C-T

Variant summary

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

The ENST00000640655.2(ENSG00000283782):​c.-637-11265C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,090 control chromosomes in the GnomAD database, including 4,763 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 0.24 (4763 hom., cov: 32)
• Consequence: ENSG00000283782 ENST00000640655.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

Genes affected

ENSG00000283782 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF1-AS1	NR_161242.1	n.272-740C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000640655.2	c.-637-11265C>T		intron_variant		5		ENSP00000491596.2

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37042 AN: 151972 Hom.: 4766 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.244 AC: 37063 AN: 152090 Hom.: 4763 Cov.: 32 AF XY: 0.248 AC XY: 18450 AN XY: 74352

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.245

Alfa AF: 0.230 Hom.: 657

Bravo AF: 0.243

Asia WGS AF: 0.370 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.23
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2706381; hg19: chr5-131810619; COSMIC: COSV66755062; COSMIC: COSV66755062;