5-132507773-A-G

Variant names:

• chr5-132507773-A-G
• rs72797327
• ENST00000638452.2:c.-168-51511A>G

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-168-51511A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,098 control chromosomes in the GnomAD database, including 4,195 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 0.23 (4195 hom., cov: 31)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 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.-168-51511A>G		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34244 AN: 151980 Hom.: 4190 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.225 AC: 34257 AN: 152098 Hom.: 4195 Cov.: 31 AF XY: 0.223 AC XY: 16603 AN XY: 74344

African (AFR) AF: 0.140 AC: 5812 AN: 41512

American (AMR) AF: 0.212 AC: 3249 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 910 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2325 AN: 5166

South Asian (SAS) AF: 0.248 AC: 1198 AN: 4822

European-Finnish (FIN) AF: 0.227 AC: 2394 AN: 10558

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17386 AN: 67966

Other (OTH) AF: 0.268 AC: 565 AN: 2106

Alfa AF: 0.183 Hom.: 587

Bravo AF: 0.225

Asia WGS AF: 0.335 AC: 1163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.44
PhyloP100		0.20

Splicing

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

Other links and lift over

dbSNP: rs72797327; hg19: chr5-131843465; COSMIC: COSV60199122;