rs2522051

Positions:

• chr5-132461886-T-C

Variant summary

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

The NR_161242.1(IRF1-AS1):​n.271+12197T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,130 control chromosomes in the GnomAD database, including 19,315 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 0.49 (19315 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: IRF1-AS1 NR_161242.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850

Genes affected

IRF1-AS1 (HGNC:33838): (colitis associated IRF1 antisense regulator of intestinal homeostasis)

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF1-AS1	NR_161242.1	n.271+12197T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF1-AS1	ENST00000612967.2	n.280+12197T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75244 AN: 152012 Hom.: 19298 Cov.: 33

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.464

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.495 AC: 75300 AN: 152130 Hom.: 19315 Cov.: 33 AF XY: 0.510 AC XY: 37933 AN XY: 74376

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.466

Alfa AF: 0.470 Hom.: 28995

Bravo AF: 0.486

Asia WGS AF: 0.739 AC: 2567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2522051; hg19: chr5-131797578;