rs2549008

chr5-132491161-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000680796.1(IRF1):c.-5-1678C>T 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: IRF1 ENST00000680796.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF1	ENST00000680796.1	c.-5-1678C>T		intron_variant
IRF1	ENST00000681584.1	c.-5-1678C>T		intron_variant
IRF1	ENST00000463784.6	n.30+193C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.0316

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.138

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2549008; hg19: chr5-131826853;