rs4705950

chr5-132457594-C-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+7905C>T 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 0.284 in 152,108 control chromosomes in the GnomAD database, including 7,713 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 0.28 (7713 hom., cov: 32)
• Consequence: IRF1-AS1 NR_161242.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF1-AS1	NR_161242.1	n.271+7905C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF1-AS1	ENST00000612967.2	n.280+7905C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43189 AN: 151990 Hom.: 7714 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.284 AC: 43200 AN: 152108 Hom.: 7713 Cov.: 32 AF XY: 0.274 AC XY: 20365 AN XY: 74348

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.0212

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.333

Alfa AF: 0.380 Hom.: 4036

Bravo AF: 0.279

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.7
Dann	Benign	0.56

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: rs4705950; hg19: chr5-131793286;