rs10067603

chr5-132468176-A-G

Variant summary

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

The ENST00000365663.1(Y_RNA):n.30A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,080 control chromosomes in the GnomAD database, including 3,099 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 0.18 (3098 hom., cov: 30)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: Y_RNA ENST00000365663.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

Genes affected

Y_RNA (HGNC:):

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF1-AS1	NR_161242.1	n.272-7491A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
Y_RNA	ENST00000365663.1	n.30A>G		non_coding_transcript_exon_variant	1/1
IRF1-AS1	ENST00000612967.2	n.281-18016A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27267 AN: 151936 Hom.: 3095 Cov.: 30

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.154 AC: 4 AN: 26 Hom.: 1 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.179 AC: 27277 AN: 152054 Hom.: 3098 Cov.: 30 AF XY: 0.186 AC XY: 13798 AN XY: 74300

Gnomad4 AFR AF: 0.0569

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.161

Alfa AF: 0.204 Hom.: 464

Bravo AF: 0.160

Asia WGS AF: 0.230 AC: 800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.8
Dann	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10067603; hg19: chr5-131803868;