dbSNP rs9282763: IRF1:c.545-68A>G (chr5-132486441-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.545-68A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,608,276 control chromosomes in the GnomAD database, including 97,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11331 hom., cov: 33)

Exomes 𝑓: 0.34 ( 85866 hom. )

Consequence

IRF1
NM_002198.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.32

Publications

20 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=-0.88).

BP6

Variant 5-132486441-T-C is Benign according to our data. Variant chr5-132486441-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688382.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 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.545-68A>G	intron	N/A	NP_002189.1	P10914
IRF1	NM_001354924.1		c.544+116A>G	intron	N/A	NP_001341853.1	X5D3F6
IRF1	NM_001354925.1		c.545-68A>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.545-68A>G	intron	N/A	ENSP00000245414.4	P10914
ENSG00000283782	ENST00000638452.2	TSL:5	c.-169+36752T>C	intron	N/A	ENSP00000492349.2	A0A1W2PQ90
CARINH	ENST00000612967.2	TSL:1	n.530T>C	non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57648

AN:

152030

Hom.:

11317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.330

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.360

GnomAD2 exomes

AF:

0.347

AC:

85735

AN:

246886

AF XY:

0.347

show subpopulations

Gnomad AFR exome

AF:

0.486

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.317

Gnomad EAS exome

AF:

0.345

Gnomad FIN exome

AF:

0.322

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.356

GnomAD4 exome

AF:

0.341

AC:

496764

AN:

1456128

Hom.:

85866

Cov.:

AF XY:

0.342

AC XY:

247669

AN XY:

724490

show subpopulations

African (AFR)

AF:

0.491

AC:

16437

AN:

33452

American (AMR)

AF:

0.331

AC:

14765

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

8254

AN:

26132

East Asian (EAS)

AF:

0.331

AC:

13116

AN:

39650

South Asian (SAS)

AF:

0.387

AC:

33267

AN:

86000

European-Finnish (FIN)

AF:

0.325

AC:

16053

AN:

49366

Middle Eastern (MID)

AF:

0.404

AC:

2329

AN:

5764

European-Non Finnish (NFE)

AF:

0.334

AC:

371475

AN:

1110792

Other (OTH)

AF:

0.349

AC:

21068

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

17394

34789

52183

69578

86972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12238

24476

36714

48952

61190

<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:

0.379

AC:

57705

AN:

152148

Hom.:

11331

Cov.:

AF XY:

0.378

AC XY:

28154

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.487

AC:

20232

AN:

41508

American (AMR)

AF:

0.343

AC:

5246

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1120

AN:

3470

East Asian (EAS)

AF:

0.361

AC:

1861

AN:

5160

South Asian (SAS)

AF:

0.410

AC:

1981

AN:

4830

European-Finnish (FIN)

AF:

0.330

AC:

3495

AN:

10596

Middle Eastern (MID)

AF:

0.486

AC:

142

AN:

292

European-Non Finnish (NFE)

AF:

0.333

AC:

22661

AN:

67986

Other (OTH)

AF:

0.360

AC:

759

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1832

3664

5495

7327

9159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.353

Hom.:

2150

Bravo

AF:

0.382

Asia WGS

AF:

0.377

AC:

1312

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

-0.88

CADD

Benign

1.1

(source)

DANN

Benign

0.42

PhyloP100

-1.3

PromoterAI

-0.014

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