Genetic Variant NM_002198.3:c.854-31A>G (chr5-132484106-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002198.3(IRF1):c.854-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,607,954 control chromosomes in the GnomAD database, including 89,455 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.34 ( 8558 hom., cov: 32)

Exomes 𝑓: 0.33 ( 80897 hom. )

Consequence

IRF1
NM_002198.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.749

Publications

19 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-132484106-T-C is Benign according to our data. Variant chr5-132484106-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688378.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002198.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IRF1	NM_002198.3	MANE Select	c.854-31A>G	intron	N/A	NP_002189.1	P10914
IRF1	NM_001354924.1		c.731-31A>G	intron	N/A	NP_001341853.1	X5D3F6
IRF1	NM_001354925.1		c.668-31A>G	intron	N/A	NP_001341854.1	A0A7P0TAL6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IRF1	ENST00000245414.9	TSL:1 MANE Select	c.854-31A>G	intron	N/A	ENSP00000245414.4	P10914
ENSG00000283782	ENST00000638452.2	TSL:5	c.-169+34417T>C	intron	N/A	ENSP00000492349.2	A0A1W2PQ90
CARINH	ENST00000612967.2	TSL:1	n.281-2086T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.337

AC:

51039

AN:

151554

Hom.:

8554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.355

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.360

Gnomad SAS

AF:

0.405

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.326

Gnomad OTH

AF:

0.332

GnomAD2 exomes

AF:

0.334

AC:

83461

AN:

249922

AF XY:

0.336

show subpopulations

Gnomad AFR exome

AF:

0.356

Gnomad AMR exome

AF:

0.317

Gnomad ASJ exome

AF:

0.313

Gnomad EAS exome

AF:

0.344

Gnomad FIN exome

AF:

0.322

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.348

GnomAD4 exome

AF:

0.332

AC:

482971

AN:

1456282

Hom.:

80897

Cov.:

AF XY:

0.333

AC XY:

241196

AN XY:

724020

show subpopulations

African (AFR)

AF:

0.361

AC:

12048

AN:

33384

American (AMR)

AF:

0.321

AC:

14311

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.311

AC:

8102

AN:

26022

East Asian (EAS)

AF:

0.330

AC:

13079

AN:

39584

South Asian (SAS)

AF:

0.384

AC:

33023

AN:

86054

European-Finnish (FIN)

AF:

0.324

AC:

17281

AN:

53294

Middle Eastern (MID)

AF:

0.389

AC:

2177

AN:

5592

European-Non Finnish (NFE)

AF:

0.328

AC:

362784

AN:

1107570

Other (OTH)

AF:

0.335

AC:

20166

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

14240

28480

42719

56959

71199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11956

23912

35868

47824

59780

<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:

0.337

AC:

51076

AN:

151672

Hom.:

8558

Cov.:

AF XY:

0.337

AC XY:

24998

AN XY:

74110

show subpopulations

African (AFR)

AF:

0.355

AC:

14662

AN:

41302

American (AMR)

AF:

0.323

AC:

4928

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1103

AN:

3466

East Asian (EAS)

AF:

0.359

AC:

1852

AN:

5158

South Asian (SAS)

AF:

0.406

AC:

1956

AN:

4814

European-Finnish (FIN)

AF:

0.323

AC:

3388

AN:

10504

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.326

AC:

22138

AN:

67862

Other (OTH)

AF:

0.332

AC:

698

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1755

3510

5266

7021

8776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.328

Hom.:

1536

Bravo

AF:

0.335

Asia WGS

AF:

0.366

AC:

1275

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.8

(source)

DANN

Benign

0.52

PhyloP100

-0.75

PromoterAI

-0.0018

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over