rs7719499

Variant names:

• chr5-132478399-C-G
• rs7719499
• ENST00000638452.2:c.-169+28710C>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+28710C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,150 control chromosomes in the GnomAD database, including 10,866 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 0.37 (10866 hom., cov: 33)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.722
• Publications: 14 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=-0.83).
• 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+28710C>G		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56286 AN: 152032 Hom.: 10851 Cov.: 33

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.370 AC: 56342 AN: 152150 Hom.: 10866 Cov.: 33 AF XY: 0.370 AC XY: 27504 AN XY: 74372

African (AFR) AF: 0.484 AC: 20102 AN: 41502

American (AMR) AF: 0.333 AC: 5083 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1091 AN: 3470

East Asian (EAS) AF: 0.359 AC: 1854 AN: 5160

South Asian (SAS) AF: 0.400 AC: 1929 AN: 4824

European-Finnish (FIN) AF: 0.326 AC: 3456 AN: 10600

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21730 AN: 67988

Other (OTH) AF: 0.353 AC: 747 AN: 2114

Alfa AF: 0.353 Hom.: 1174

Bravo AF: 0.374

Asia WGS AF: 0.372 AC: 1295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
DANN	Benign	0.73
PhyloP100		0.72

Splicing

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

Other links and lift over

dbSNP: rs7719499; hg19: chr5-131814091;