rs4705952

Variant names:

• chr5-132503926-G-A
• rs4705952
• ENST00000638452.2:c.-169+54237G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000638452.2(ENSG00000283782):​c.-169+54237G>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 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• Publications: 37 publications found

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]

IRF1 Gene-Disease associations (from GenCC):

• immunodeficiency 117

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000638452.2	c.-169+54237G>A		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

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

African (AFR) AF: 0.384 AC: 15855 AN: 41314

American (AMR) AF: 0.760 AC: 11603 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2393 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2174 AN: 5118

South Asian (SAS) AF: 0.546 AC: 2625 AN: 4804

European-Finnish (FIN) AF: 0.650 AC: 6845 AN: 10530

Middle Eastern (MID) AF: 0.651 AC: 190 AN: 292

European-Non Finnish (NFE) AF: 0.740 AC: 50243 AN: 67894

Other (OTH) AF: 0.674 AC: 1418 AN: 2104

Alfa AF: 0.704 Hom.: 147328

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
PhyloP100		-0.25

Splicing

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

Other links and lift over

dbSNP: rs4705952; hg19: chr5-131839618;