ENST00000638452.2:c.-169+47306C>T

Variant names:

• chr5-132496995-C-T
• rs2706386
• ENST00000638452.2:c.-169+47306C>T

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-169+47306C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,202 control chromosomes in the GnomAD database, including 27,931 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 0.60 (27931 hom., cov: 35)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.661 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+47306C>T		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90691 AN: 152086 Hom.: 27917 Cov.: 35

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.596 AC: 90734 AN: 152202 Hom.: 27931 Cov.: 35 AF XY: 0.598 AC XY: 44486 AN XY: 74410

African (AFR) AF: 0.426 AC: 17690 AN: 41518

American (AMR) AF: 0.645 AC: 9880 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2321 AN: 3470

East Asian (EAS) AF: 0.655 AC: 3383 AN: 5166

South Asian (SAS) AF: 0.590 AC: 2851 AN: 4830

European-Finnish (FIN) AF: 0.672 AC: 7122 AN: 10604

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45316 AN: 67990

Other (OTH) AF: 0.624 AC: 1318 AN: 2112

Alfa AF: 0.513 Hom.: 1523

Bravo AF: 0.589

Asia WGS AF: 0.624 AC: 2169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.3
DANN	Benign	0.97
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs2706386; hg19: chr5-131832687;