rs4705862

Positions:

• chr5-132477527-A-T

Variant summary

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

The ENST00000612967.2(IRF1-AS1):​n.281-8665A>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 0.513 in 152,092 control chromosomes in the GnomAD database, including 20,672 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 0.51 (20672 hom., cov: 33)
• Consequence: IRF1-AS1 ENST00000612967.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.666

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.677 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-AS1	ENST00000612967.2	n.281-8665A>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77875 AN: 151974 Hom.: 20636 Cov.: 33

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.513 AC: 77970 AN: 152092 Hom.: 20672 Cov.: 33 AF XY: 0.520 AC XY: 38669 AN XY: 74354

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.485

Alfa AF: 0.481 Hom.: 2242

Bravo AF: 0.518

Asia WGS AF: 0.619 AC: 2155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4705862; hg19: chr5-131813219;