rs2706390

Variant names:

• chr5-132506588-C-A
• rs2706390
• ENST00000638452.2:c.-168-52696C>A

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-168-52696C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 151,912 control chromosomes in the GnomAD database, including 2,805 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 0.19 (2805 hom., cov: 32)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-168-52696C>A		intron	N/A	ENSP00000492349.2
	ENSG00000283782	ENST00000638568.2	TSL:5	c.-310-49744C>A		intron	N/A	ENSP00000491158.2
	ENSG00000283782	ENST00000640655.2	TSL:5	c.-169+19928C>A		intron	N/A	ENSP00000491596.2

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28725 AN: 151792 Hom.: 2803 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.154

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.189 AC: 28738 AN: 151912 Hom.: 2805 Cov.: 32 AF XY: 0.190 AC XY: 14122 AN XY: 74234

African (AFR) AF: 0.197 AC: 8159 AN: 41412

American (AMR) AF: 0.144 AC: 2203 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 807 AN: 3470

East Asian (EAS) AF: 0.141 AC: 726 AN: 5166

South Asian (SAS) AF: 0.215 AC: 1034 AN: 4820

European-Finnish (FIN) AF: 0.234 AC: 2459 AN: 10504

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12851 AN: 67958

Other (OTH) AF: 0.168 AC: 353 AN: 2106

Alfa AF: 0.196 Hom.: 899

Bravo AF: 0.179

Asia WGS AF: 0.173 AC: 601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.31
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs2706390; hg19: chr5-131842280;