rs6874639

Variant names:

• chr5-132443024-A-G
• rs6874639
• ENST00000638452.2:c.-208-6626A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-132443024-A-G
• chr5-132443024-A-T

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-208-6626A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,130 control chromosomes in the GnomAD database, including 4,918 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 (4918 hom., cov: 32)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 19 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000638452.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARINH	NR_161242.1		n.232-6626A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-208-6626A>G		intron	N/A	ENSP00000492349.2
	CARINH	ENST00000612967.2	TSL:1	n.241-6626A>G		intron	N/A
	ENSG00000283782	ENST00000638568.2	TSL:5	c.-350-6626A>G		intron	N/A	ENSP00000491158.2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37566 AN: 152012 Hom.: 4918 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.247 AC: 37593 AN: 152130 Hom.: 4918 Cov.: 32 AF XY: 0.252 AC XY: 18715 AN XY: 74366

African (AFR) AF: 0.298 AC: 12351 AN: 41478

American (AMR) AF: 0.201 AC: 3075 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 888 AN: 3460

East Asian (EAS) AF: 0.391 AC: 2019 AN: 5170

South Asian (SAS) AF: 0.399 AC: 1921 AN: 4820

European-Finnish (FIN) AF: 0.223 AC: 2359 AN: 10590

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14320 AN: 67998

Other (OTH) AF: 0.243 AC: 513 AN: 2114

Alfa AF: 0.237 Hom.: 859

Bravo AF: 0.244

Asia WGS AF: 0.384 AC: 1335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.64
DANN	Benign	0.56
PhyloP100		0.047

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: rs6874639; hg19: chr5-131778716; COSMIC: COSV61819976;