Genetic Variant ENSG00000283782:c.-169+12166A>G (chr5-132461855-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000638452.2(ENSG00000283782):c.-169+12166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,142 control chromosomes in the GnomAD database, including 16,085 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 0.45 ( 16083 hom., cov: 33)

Exomes 𝑓: 0.83 ( 2 hom. )

Consequence

ENSG00000283782
ENST00000638452.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.472

Publications

38 publications found

Variant links:

Genes affected

ENSG00000283782 (HGNC:):

ENSG00000283782 links:

CARINH (HGNC:33838): (colitis associated IRF1 antisense regulator of intestinal homeostasis)

CARINH links:

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

IRF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARINH	NR_161242.1 link	n.271+12166A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000638452.2 link	c.-169+12166A>G		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68784

AN:

152018

Hom.:

16055

Cov.:

show subpopulations

Gnomad AFR

AF:

0.541

Gnomad AMI

AF:

0.312

Gnomad AMR

AF:

0.496

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.594

Gnomad SAS

AF:

0.492

Gnomad FIN

AF:

0.470

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.381

Gnomad OTH

AF:

0.413

GnomAD4 exome

AF:

0.833

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.453

AC:

68866

AN:

152136

Hom.:

16083

Cov.:

AF XY:

0.459

AC XY:

34106

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.542

AC:

22477

AN:

41490

American (AMR)

AF:

0.496

AC:

7588

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1200

AN:

3472

East Asian (EAS)

AF:

0.593

AC:

3076

AN:

5188

South Asian (SAS)

AF:

0.492

AC:

2372

AN:

4826

European-Finnish (FIN)

AF:

0.470

AC:

4962

AN:

10556

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.381

AC:

25885

AN:

67990

Other (OTH)

AF:

0.413

AC:

873

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1930

3861

5791

7722

9652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.413

Hom.:

8212

Bravo

AF:

0.456

Asia WGS

AF:

0.519

AC:

1803

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.9

(source)

DANN

Benign

0.47

PhyloP100

0.47

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over