ENST00000638452.2:c.-169+10216A>G

Variant names:

• chr5-132459905-A-G
• rs886286
• ENST00000638452.2:c.-169+10216A>G

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-169+10216A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,098 control chromosomes in the GnomAD database, including 5,157 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 (5157 hom., cov: 32)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARINH	NR_161242.1	n.271+10216A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000638452.2	c.-169+10216A>G		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38495 AN: 151980 Hom.: 5159 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.253 AC: 38522 AN: 152098 Hom.: 5157 Cov.: 32 AF XY: 0.258 AC XY: 19185 AN XY: 74352

African (AFR) AF: 0.310 AC: 12877 AN: 41482

American (AMR) AF: 0.210 AC: 3205 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2079 AN: 5166

South Asian (SAS) AF: 0.386 AC: 1861 AN: 4826

European-Finnish (FIN) AF: 0.222 AC: 2344 AN: 10578

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14560 AN: 67974

Other (OTH) AF: 0.250 AC: 528 AN: 2110

Alfa AF: 0.242 Hom.: 605

Bravo AF: 0.253

Asia WGS AF: 0.385 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.027
DANN	Benign	0.22
PhyloP100		-2.7

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

Other links and lift over

dbSNP: rs886286; hg19: chr5-131795597;