rs12521868

Variant names:

• chr5-132448701-G-T
• rs12521868
• ENST00000638452.2:c.-208-949G>T

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-208-949G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,096 control chromosomes in the GnomAD database, including 7,676 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 0.28 (7676 hom., cov: 32)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 102 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARINH	NR_161242.1	n.232-949G>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000638452.2	c.-208-949G>T		intron_variant	Intron 2 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42696 AN: 151978 Hom.: 7678 Cov.: 32

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.281 AC: 42689 AN: 152096 Hom.: 7676 Cov.: 32 AF XY: 0.270 AC XY: 20107 AN XY: 74346

African (AFR) AF: 0.0930 AC: 3861 AN: 41500

American (AMR) AF: 0.293 AC: 4486 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1359 AN: 3468

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5186

South Asian (SAS) AF: 0.109 AC: 524 AN: 4820

European-Finnish (FIN) AF: 0.310 AC: 3268 AN: 10556

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27882 AN: 67964

Other (OTH) AF: 0.323 AC: 681 AN: 2110

Alfa AF: 0.369 Hom.: 47062

Bravo AF: 0.275

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.80
PhyloP100		-0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12521868; hg19: chr5-131784393;