rs2522051

Variant names:

• chr5-132461886-T-C
• rs2522051
• ENST00000638452.2:c.-169+12197T>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+12197T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,130 control chromosomes in the GnomAD database, including 19,315 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 0.49 (19315 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850
• Publications: 27 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARINH	NR_161242.1	n.271+12197T>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000638452.2	c.-169+12197T>C		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75244 AN: 152012 Hom.: 19298 Cov.: 33

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.464

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.495 AC: 75300 AN: 152130 Hom.: 19315 Cov.: 33 AF XY: 0.510 AC XY: 37933 AN XY: 74376

African (AFR) AF: 0.434 AC: 17994 AN: 41490

American (AMR) AF: 0.573 AC: 8760 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1452 AN: 3472

East Asian (EAS) AF: 0.736 AC: 3813 AN: 5182

South Asian (SAS) AF: 0.790 AC: 3817 AN: 4832

European-Finnish (FIN) AF: 0.588 AC: 6205 AN: 10560

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31924 AN: 67984

Other (OTH) AF: 0.466 AC: 984 AN: 2112

Alfa AF: 0.473 Hom.: 65381

Bravo AF: 0.486

Asia WGS AF: 0.739 AC: 2567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.53
PhyloP100		-0.85

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: rs2522051; hg19: chr5-131797578;