rs4705861

Positions:

• chr5-132465072-T-C

Variant summary

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

The ENST00000640655.2(ENSG00000283782):​c.-638+15383T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 152,392 control chromosomes in the GnomAD database, including 467 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 0.054 (467 hom., cov: 33)
  • Exomes 𝑓: 0.040 (0 hom.)
• Consequence: ENSG00000283782 ENST00000640655.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF1-AS1	NR_161242.1	n.272-10595T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000640655.2	c.-638+15383T>C		intron_variant		5		ENSP00000491596.2

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8185 AN: 152174 Hom.: 468 Cov.: 33

Gnomad AFR AF: 0.0459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.0777

Gnomad FIN AF: 0.0485

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0250

Gnomad OTH AF: 0.0478

GnomAD4 exome AF: 0.0400 AC: 4 AN: 100 Hom.: 0 Cov.: 0 AF XY: 0.0429 AC XY: 3 AN XY: 70

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0385

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0538 AC: 8195 AN: 152292 Hom.: 467 Cov.: 33 AF XY: 0.0590 AC XY: 4392 AN XY: 74464

Gnomad4 AFR AF: 0.0460

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.0767

Gnomad4 FIN AF: 0.0485

Gnomad4 NFE AF: 0.0250

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0399 Hom.: 30

Bravo AF: 0.0641

Asia WGS AF: 0.118 AC: 410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0060
DANN	Benign	0.50

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: rs4705861; hg19: chr5-131800764;