rs10065633

Variant names:

• chr5-132481024-T-C
• rs10065633
• ENST00000638452.2:c.-169+31335T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000638452.2(ENSG00000283782):​c.-169+31335T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,838 control chromosomes in the GnomAD database, including 11,104 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 0.38 (11104 hom., cov: 32)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.947
• Publications: 13 publications found

Genes affected

ENSG00000283782 (HGNC:):

CARINH (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]

IRF1 Gene-Disease associations (from GenCC):

• immunodeficiency 117

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000638452.2	c.-169+31335T>C		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57122 AN: 151718 Hom.: 11089 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.377 AC: 57181 AN: 151838 Hom.: 11104 Cov.: 32 AF XY: 0.376 AC XY: 27903 AN XY: 74242

African (AFR) AF: 0.485 AC: 20039 AN: 41346

American (AMR) AF: 0.342 AC: 5226 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1103 AN: 3470

East Asian (EAS) AF: 0.358 AC: 1848 AN: 5160

South Asian (SAS) AF: 0.410 AC: 1980 AN: 4828

European-Finnish (FIN) AF: 0.327 AC: 3456 AN: 10558

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22425 AN: 67886

Other (OTH) AF: 0.359 AC: 757 AN: 2108

Alfa AF: 0.367 Hom.: 1330

Bravo AF: 0.381

Asia WGS AF: 0.375 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.58
DANN	Benign	0.49
PhyloP100		-0.95

Splicing

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

Other links and lift over

dbSNP: rs10065633; hg19: chr5-131816716;