rs6874639

chr5-132443024-A-Gchr5-132443024-A-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.232-6626A>G 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 0.247 in 152,130 control chromosomes in the GnomAD database, including 4,918 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 0.25 (4918 hom., cov: 32)
• Consequence: IRF1-AS1 NR_161242.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

Genes affected

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

LOC124901064 (HGNC:):

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF1-AS1	NR_161242.1	n.232-6626A>G		intron_variant, non_coding_transcript_variant
LOC124901064	XR_007058935.1	n.81-2356T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF1-AS1	ENST00000612967.2	n.241-6626A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37566 AN: 152012 Hom.: 4918 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.247 AC: 37593 AN: 152130 Hom.: 4918 Cov.: 32 AF XY: 0.252 AC XY: 18715 AN XY: 74366

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.243

Alfa AF: 0.236 Hom.: 832

Bravo AF: 0.244

Asia WGS AF: 0.384 AC: 1335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.64
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: rs6874639; hg19: chr5-131778716; COSMIC: COSV61819976;