dbSNP rs2070728: IRF1:c.853+77G>A (chr5-132484285-C-T) – 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.853+77G>A 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 1,517,494 control chromosomes in the GnomAD database, including 85,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11085 hom., cov: 31)

Exomes 𝑓: 0.33 ( 74633 hom. )

Consequence

IRF1
NM_002198.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.183

Publications

21 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=-0.79).

BP6

Variant 5-132484285-C-T is Benign according to our data. Variant chr5-132484285-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688399.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 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.853+77G>A	intron	N/A	NP_002189.1	P10914
IRF1	NM_001354924.1		c.730+77G>A	intron	N/A	NP_001341853.1	X5D3F6
IRF1	NM_001354925.1		c.668-210G>A	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.853+77G>A	intron	N/A	ENSP00000245414.4	P10914
ENSG00000283782	ENST00000638452.2	TSL:5	c.-169+34596C>T	intron	N/A	ENSP00000492349.2	A0A1W2PQ90
CARINH	ENST00000612967.2	TSL:1	n.281-1907C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

56982

AN:

151372

Hom.:

11071

Cov.:

show subpopulations

Gnomad AFR

AF:

0.484

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.359

GnomAD4 exome

AF:

0.327

AC:

447316

AN:

1366004

Hom.:

74633

Cov.:

AF XY:

0.329

AC XY:

222980

AN XY:

678514

show subpopulations

African (AFR)

AF:

0.478

AC:

14629

AN:

30614

American (AMR)

AF:

0.317

AC:

12790

AN:

40370

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

6878

AN:

23138

East Asian (EAS)

AF:

0.328

AC:

12784

AN:

38996

South Asian (SAS)

AF:

0.375

AC:

29590

AN:

78984

European-Finnish (FIN)

AF:

0.325

AC:

16764

AN:

51538

Middle Eastern (MID)

AF:

0.391

AC:

2097

AN:

5370

European-Non Finnish (NFE)

AF:

0.320

AC:

332621

AN:

1040198

Other (OTH)

AF:

0.337

AC:

19163

AN:

56796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

12487

24973

37460

49946

62433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10954

21908

32862

43816

54770

<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:

0.377

AC:

57039

AN:

151490

Hom.:

11085

Cov.:

AF XY:

0.375

AC XY:

27764

AN XY:

73982

show subpopulations

African (AFR)

AF:

0.484

AC:

19951

AN:

41194

American (AMR)

AF:

0.342

AC:

5215

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1100

AN:

3456

East Asian (EAS)

AF:

0.358

AC:

1830

AN:

5118

South Asian (SAS)

AF:

0.409

AC:

1970

AN:

4812

European-Finnish (FIN)

AF:

0.327

AC:

3443

AN:

10536

Middle Eastern (MID)

AF:

0.479

AC:

139

AN:

290

European-Non Finnish (NFE)

AF:

0.331

AC:

22429

AN:

67822

Other (OTH)

AF:

0.359

AC:

755

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1645

3290

4934

6579

8224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.367

Hom.:

1342

Bravo

AF:

0.381

Asia WGS

AF:

0.376

AC:

1306

AN:

3476

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

-0.79

CADD

Benign

3.6

(source)

DANN

Benign

0.74

PhyloP100

-0.18

PromoterAI

-0.041

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over