chr5-132507614-T-C

Variant names:

• chr5-132507614-T-C
• rs2706391
• ENST00000638452.2:c.-168-51670T>C

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-168-51670T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,914 control chromosomes in the GnomAD database, including 2,032 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 0.15 (2032 hom., cov: 31)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000638452.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-168-51670T>C		intron	N/A	ENSP00000492349.2
	ENSG00000283782	ENST00000638568.2	TSL:5	c.-310-48718T>C		intron	N/A	ENSP00000491158.2
	ENSG00000283782	ENST00000640655.2	TSL:5	c.-169+20954T>C		intron	N/A	ENSP00000491596.2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22501 AN: 151794 Hom.: 2030 Cov.: 31

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.148 AC: 22507 AN: 151914 Hom.: 2032 Cov.: 31 AF XY: 0.151 AC XY: 11185 AN XY: 74252

African (AFR) AF: 0.0556 AC: 2305 AN: 41484

American (AMR) AF: 0.131 AC: 1994 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3470

East Asian (EAS) AF: 0.140 AC: 724 AN: 5170

South Asian (SAS) AF: 0.214 AC: 1030 AN: 4820

European-Finnish (FIN) AF: 0.233 AC: 2430 AN: 10442

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12793 AN: 67956

Other (OTH) AF: 0.147 AC: 309 AN: 2100

Alfa AF: 0.145 Hom.: 813

Bravo AF: 0.132

Asia WGS AF: 0.166 AC: 577 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.33
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs2706391; hg19: chr5-131843306;