rs2549005

Variant names:

• chr5-132491499-T-C
• rs2549005
• ENST00000638452.2:c.-169+41810T>C

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-169+41810T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,116 control chromosomes in the GnomAD database, including 31,000 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 0.64 (31000 hom., cov: 33)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503
• Publications: 14 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 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+41810T>C		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96708 AN: 151998 Hom.: 30975 Cov.: 33

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.636 AC: 96786 AN: 152116 Hom.: 31000 Cov.: 33 AF XY: 0.637 AC XY: 47375 AN XY: 74368

African (AFR) AF: 0.556 AC: 23057 AN: 41480

American (AMR) AF: 0.668 AC: 10207 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2352 AN: 3472

East Asian (EAS) AF: 0.640 AC: 3309 AN: 5172

South Asian (SAS) AF: 0.593 AC: 2859 AN: 4822

European-Finnish (FIN) AF: 0.674 AC: 7133 AN: 10586

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

European-Non Finnish (NFE) AF: 0.671 AC: 45641 AN: 67982

Other (OTH) AF: 0.651 AC: 1375 AN: 2112

Alfa AF: 0.642 Hom.: 5469

Bravo AF: 0.635

Asia WGS AF: 0.629 AC: 2185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.3
DANN	Benign	0.71
PhyloP100		-0.50

Splicing

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

Other links and lift over

dbSNP: rs2549005; hg19: chr5-131827191; COSMIC: COSV55376715; COSMIC: COSV55376715;