Genetic Variant ENSG00000283782:c.-169+11541G>A (chr5-132461230-G-A) – 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+11541G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 176,616 control chromosomes in the GnomAD database, including 13,106 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 0.39 ( 11576 hom., cov: 33)

Exomes 𝑓: 0.34 ( 1530 hom. )

Consequence

ENSG00000283782
ENST00000638452.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

Publications

39 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARINH	NR_161242.1 link	n.271+11541G>A		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+11541G>A		intron_variant	Intron 3 of 26	5		ENSP00000492349.2		A0A1W2PQ90

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58781

AN:

151938

Hom.:

11556

Cov.:

show subpopulations

Gnomad AFR

AF:

0.475

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.404

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.358

GnomAD4 exome

AF:

0.339

AC:

8325

AN:

24560

Hom.:

1530

Cov.:

AF XY:

0.339

AC XY:

4441

AN XY:

13102

show subpopulations

African (AFR)

AF:

0.452

AC:

246

AN:

544

American (AMR)

AF:

0.308

AC:

928

AN:

3016

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

AN:

426

East Asian (EAS)

AF:

0.309

AC:

487

AN:

1578

South Asian (SAS)

AF:

0.382

AC:

1671

AN:

4372

European-Finnish (FIN)

AF:

0.374

AC:

193

AN:

516

Middle Eastern (MID)

AF:

0.423

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

4281

AN:

12852

Other (OTH)

AF:

0.334

AC:

393

AN:

1178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

268

537

805

1074

1342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.387

AC:

58842

AN:

152056

Hom.:

11576

Cov.:

AF XY:

0.389

AC XY:

28882

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.475

AC:

19709

AN:

41474

American (AMR)

AF:

0.340

AC:

5186

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

1067

AN:

3470

East Asian (EAS)

AF:

0.338

AC:

1750

AN:

5176

South Asian (SAS)

AF:

0.404

AC:

1948

AN:

4820

European-Finnish (FIN)

AF:

0.421

AC:

4448

AN:

10558

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.346

AC:

23548

AN:

67974

Other (OTH)

AF:

0.357

AC:

755

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1896

3791

5687

7582

9478

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<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:

0.355

Hom.:

34395

Bravo

AF:

0.379

Asia WGS

AF:

0.381

AC:

1327

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.029

(source)

DANN

Benign

0.43

PhyloP100

-1.5

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