Genetic Variant IRF1:c.*517G>A (chr5-132483434-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002198.3(IRF1):c.*517G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 153,326 control chromosomes in the GnomAD database, including 11,323 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 ( 11254 hom., cov: 32)

Exomes 𝑓: 0.32 ( 69 hom. )

Consequence

IRF1
NM_002198.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

Publications

31 publications found

Variant links:

Genes affected

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 links:

ENSG00000283782 (HGNC:):

ENSG00000283782 links:

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

CARINH 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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF1	NM_002198.3 link	c.*517G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000245414.9	NP_002189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9 link	c.*517G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_002198.3	ENSP00000245414.4
ENSG00000283782	ENST00000638452.2 link	c.-169+33745C>T		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57438

AN:

151944

Hom.:

11240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.486

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.330

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.359

GnomAD4 exome

AF:

0.317

AC:

401

AN:

1264

Hom.:

Cov.:

AF XY:

0.313

AC XY:

233

AN XY:

744

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.375

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.429

AC:

AN:

126

South Asian (SAS)

AF:

0.321

AC:

AN:

274

European-Finnish (FIN)

AF:

0.319

AC:

134

AN:

420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.272

AC:

100

AN:

368

Other (OTH)

AF:

0.269

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.378

AC:

57495

AN:

152062

Hom.:

11254

Cov.:

AF XY:

0.377

AC XY:

28058

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.487

AC:

20170

AN:

41448

American (AMR)

AF:

0.343

AC:

5240

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1102

AN:

3466

East Asian (EAS)

AF:

0.361

AC:

1865

AN:

5172

South Asian (SAS)

AF:

0.410

AC:

1977

AN:

4820

European-Finnish (FIN)

AF:

0.330

AC:

3490

AN:

10582

Middle Eastern (MID)

AF:

0.490

AC:

143

AN:

292

European-Non Finnish (NFE)

AF:

0.332

AC:

22543

AN:

67974

Other (OTH)

AF:

0.359

AC:

757

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1842

3684

5526

7368

9210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

550

1100

1650

2200

2750

<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:

0.325

Hom.:

3657

Bravo

AF:

0.381

Asia WGS

AF:

0.376

AC:

1308

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.11

(source)

DANN

Benign

0.44

PhyloP100

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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