rs3749834

Positions:

• chr5-132463928-G-A
• chr5-132463928-G-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.272-11739G>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 0.207 in 152,170 control chromosomes in the GnomAD database, including 4,577 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 0.21 (4577 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: 0.586

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF1-AS1	NR_161242.1	n.272-11739G>A		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+14239G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31456 AN: 152052 Hom.: 4560 Cov.: 33

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.0804

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.196

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: 0.207 AC: 31507 AN: 152170 Hom.: 4577 Cov.: 33 AF XY: 0.202 AC XY: 15056 AN XY: 74410

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.0799

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.195

Alfa AF: 0.0778 Hom.: 116

Bravo AF: 0.219

Asia WGS AF: 0.154 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.67

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: rs3749834; hg19: chr5-131799620;