rs11745587

Positions:

• chr5-132461230-G-A
• chr5-132461230-G-C
• chr5-132461230-G-T

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+11541G>A 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 0.38 in 176,616 control chromosomes in the GnomAD database, including 13,106 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 0.39 (11576 hom., cov: 33)
  • Exomes 𝑓: 0.34 (1530 hom.)
• Consequence: IRF1-AS1 NR_161242.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF1-AS1	NR_161242.1	n.271+11541G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF1-AS1	ENST00000612967.2	n.280+11541G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58781 AN: 151938 Hom.: 11556 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.358

GnomAD4 exome AF: 0.339 AC: 8325 AN: 24560 Hom.: 1530 Cov.: 0 AF XY: 0.339 AC XY: 4441 AN XY: 13102

Gnomad4 AFR exome AF: 0.452

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.218

Gnomad4 EAS exome AF: 0.309

Gnomad4 SAS exome AF: 0.382

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.334

GnomAD4 genome AF: 0.387 AC: 58842 AN: 152056 Hom.: 11576 Cov.: 33 AF XY: 0.389 AC XY: 28882 AN XY: 74304

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.357

Alfa AF: 0.348 Hom.: 20779

Bravo AF: 0.379

Asia WGS AF: 0.381 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.029
DANN	Benign	0.43

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: rs11745587; hg19: chr5-131796922;