ENST00000612967.2:n.2461T>A

Variant names:

• chr5-132488372-T-A
• rs10213701
• ENST00000612967.2:n.2461T>A

Variant summary

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

The ENST00000612967.2(CARINH):​n.2461T>A 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 0.328 in 234,510 control chromosomes in the GnomAD database, including 12,909 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 0.34 (8742 hom., cov: 32)
  • Exomes 𝑓: 0.31 (4167 hom.)
• Consequence: CARINH ENST00000612967.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 10 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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF1	NM_002198.3	c.88-347A>T		intron_variant	Intron 2 of 9	ENST00000245414.9	NP_002189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9	c.88-347A>T		intron_variant	Intron 2 of 9	1	NM_002198.3	ENSP00000245414.4
ENSG00000283782	ENST00000638452.2	c.-169+38683T>A		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51475 AN: 151920 Hom.: 8738 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.308 AC: 25375 AN: 82472 Hom.: 4167 Cov.: 0 AF XY: 0.312 AC XY: 13907 AN XY: 44576

African (AFR) AF: 0.315 AC: 861 AN: 2730

American (AMR) AF: 0.301 AC: 1318 AN: 4384

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 634 AN: 2044

East Asian (EAS) AF: 0.308 AC: 1164 AN: 3784

South Asian (SAS) AF: 0.343 AC: 5034 AN: 14656

European-Finnish (FIN) AF: 0.293 AC: 1002 AN: 3414

Middle Eastern (MID) AF: 0.328 AC: 101 AN: 308

European-Non Finnish (NFE) AF: 0.297 AC: 13927 AN: 46878

Other (OTH) AF: 0.312 AC: 1334 AN: 4274

GnomAD4 genome AF: 0.339 AC: 51512 AN: 152038 Hom.: 8742 Cov.: 32 AF XY: 0.340 AC XY: 25233 AN XY: 74322

African (AFR) AF: 0.357 AC: 14782 AN: 41418

American (AMR) AF: 0.324 AC: 4944 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3470

East Asian (EAS) AF: 0.361 AC: 1871 AN: 5180

South Asian (SAS) AF: 0.406 AC: 1960 AN: 4822

European-Finnish (FIN) AF: 0.326 AC: 3447 AN: 10576

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22332 AN: 67980

Other (OTH) AF: 0.333 AC: 705 AN: 2114

Alfa AF: 0.210 Hom.: 434

Bravo AF: 0.336

Asia WGS AF: 0.367 AC: 1279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.5
DANN	Benign	0.82
PhyloP100		-0.29
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: rs10213701; hg19: chr5-131824064;