rs2070723

Variant names:

• chr5-132487495-A-G
• rs2070723
• ENST00000612967.2:n.1584A>G

Variant summary

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

The ENST00000612967.2(CARINH):​n.1584A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 342,484 control chromosomes in the GnomAD database, including 22,692 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 0.38 (11319 hom., cov: 32)
  • Exomes 𝑓: 0.34 (11373 hom.)
• Consequence: CARINH ENST00000612967.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 8 publications found

Genes affected

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

ENSG00000283782 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF1	NM_002198.3	c.188-365T>C		intron_variant	Intron 3 of 9	ENST00000245414.9	NP_002189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9	c.188-365T>C		intron_variant	Intron 3 of 9	1	NM_002198.3	ENSP00000245414.4
ENSG00000283782	ENST00000638452.2	c.-169+37806A>G		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57591 AN: 151930 Hom.: 11305 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.337 AC: 64185 AN: 190436 Hom.: 11373 Cov.: 0 AF XY: 0.339 AC XY: 34465 AN XY: 101550

African (AFR) AF: 0.486 AC: 3217 AN: 6624

American (AMR) AF: 0.325 AC: 2299 AN: 7082

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1705 AN: 5502

East Asian (EAS) AF: 0.330 AC: 3336 AN: 10124

South Asian (SAS) AF: 0.377 AC: 10379 AN: 27544

European-Finnish (FIN) AF: 0.327 AC: 2889 AN: 8836

Middle Eastern (MID) AF: 0.372 AC: 298 AN: 800

European-Non Finnish (NFE) AF: 0.322 AC: 36495 AN: 113412

Other (OTH) AF: 0.339 AC: 3567 AN: 10512

GnomAD4 genome AF: 0.379 AC: 57648 AN: 152048 Hom.: 11319 Cov.: 32 AF XY: 0.378 AC XY: 28124 AN XY: 74324

African (AFR) AF: 0.487 AC: 20201 AN: 41456

American (AMR) AF: 0.343 AC: 5243 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3468

East Asian (EAS) AF: 0.361 AC: 1864 AN: 5164

South Asian (SAS) AF: 0.410 AC: 1979 AN: 4824

European-Finnish (FIN) AF: 0.329 AC: 3486 AN: 10580

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.333 AC: 22645 AN: 67962

Other (OTH) AF: 0.360 AC: 759 AN: 2108

Alfa AF: 0.363 Hom.: 1250

Bravo AF: 0.382

Asia WGS AF: 0.377 AC: 1311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.15
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2070723; hg19: chr5-131823187;