rs4705952

Positions:

• chr5-132503926-G-A

Variant summary

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

The ENST00000640655.2(ENSG00000283782):​c.-169+17266G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 151,714 control chromosomes in the GnomAD database, including 31,337 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 0.62 (31337 hom., cov: 30)
• Consequence: ENSG00000283782 ENST00000640655.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.132503926G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000640655.2	c.-169+17266G>A		intron_variant		5		ENSP00000491596.2

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94091 AN: 151596 Hom.: 31321 Cov.: 30

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.677

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

GnomAD4 genome AF: 0.621 AC: 94146 AN: 151714 Hom.: 31337 Cov.: 30 AF XY: 0.616 AC XY: 45661 AN XY: 74142

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.674

Alfa AF: 0.722 Hom.: 73757

Bravo AF: 0.620

Asia WGS AF: 0.488 AC: 1696 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.9
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4705952; hg19: chr5-131839618;