5-132491073-T-C

Variant names:

• chr5-132491073-T-C
• rs2549009
• ENST00000638452.2:c.-169+41384T>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+41384T>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 152,066 control chromosomes in the GnomAD database, including 30,960 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 (30960 hom., cov: 34)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808
• 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=-1.17).
• 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+41384T>C		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96633 AN: 151948 Hom.: 30935 Cov.: 34

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.636 AC: 96711 AN: 152066 Hom.: 30960 Cov.: 34 AF XY: 0.637 AC XY: 47348 AN XY: 74372

African (AFR) AF: 0.556 AC: 23086 AN: 41512

American (AMR) AF: 0.666 AC: 10180 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2350 AN: 3468

East Asian (EAS) AF: 0.639 AC: 3285 AN: 5142

South Asian (SAS) AF: 0.592 AC: 2857 AN: 4822

European-Finnish (FIN) AF: 0.673 AC: 7137 AN: 10602

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

European-Non Finnish (NFE) AF: 0.671 AC: 45590 AN: 67904

Other (OTH) AF: 0.649 AC: 1373 AN: 2114

Alfa AF: 0.564 Hom.: 1801

Bravo AF: 0.635

Asia WGS AF: 0.627 AC: 2178 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
CADD	Benign	5.6
DANN	Benign	0.70
PhyloP100		-0.81
PromoterAI		-0.035	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2549009; hg19: chr5-131826765;