rs2549005

Positions:

• chr5-132491499-T-C

Variant summary

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

The ENST00000680796.1(IRF1):​c.-5-2016A>G 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: IRF1 ENST00000680796.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503

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 (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000680796.1	c.-5-2016A>G		intron_variant				ENSP00000506572
IRF1	ENST00000681584.1	c.-5-2016A>G		intron_variant				ENSP00000505448
IRF1	ENST00000679522.1	n.76+12A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.651

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

Splicing

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

Publications

LitVar

Other links and lift over

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