rs2549008

Variant names:

• chr5-132491161-G-A
• rs2549008
• ENST00000638452.2:c.-169+41472G>A

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-169+41472G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,194 control chromosomes in the GnomAD database, including 1,942 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 0.14 (1942 hom., cov: 34)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 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+41472G>A		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21586 AN: 152076 Hom.: 1939 Cov.: 34

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.142 AC: 21592 AN: 152194 Hom.: 1942 Cov.: 34 AF XY: 0.145 AC XY: 10757 AN XY: 74404

African (AFR) AF: 0.0316 AC: 1315 AN: 41568

American (AMR) AF: 0.131 AC: 2008 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3472

East Asian (EAS) AF: 0.110 AC: 570 AN: 5168

South Asian (SAS) AF: 0.207 AC: 1000 AN: 4820

European-Finnish (FIN) AF: 0.240 AC: 2546 AN: 10604

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12935 AN: 67940

Other (OTH) AF: 0.138 AC: 291 AN: 2112

Alfa AF: 0.179 Hom.: 345

Bravo AF: 0.126

Asia WGS AF: 0.158 AC: 550 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	7.4
DANN	Benign	0.91
PhyloP100		0.58
PromoterAI		-0.039	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2549008; hg19: chr5-131826853;