rs2070724

Variant names:

Variant summary

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

The NM_002198.3(IRF1):c.545-7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,610,364 control chromosomes in the GnomAD database, including 97,385 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11305 hom., cov: 33)

Exomes 𝑓: 0.34 ( 86080 hom. )

Consequence

IRF1
NM_002198.3 splice_region, intron

Scores

Splicing: ADA: 0.00001620

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.132

Publications

26 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=-0.86).

BP6

Variant 5-132486380-A-G is Benign according to our data. Variant chr5-132486380-A-G is described in ClinVar as Benign. ClinVar VariationId is 2688381.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 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.545-7T>C	splice_region intron	N/A	NP_002189.1	P10914
IRF1	NM_001354924.1		c.544+177T>C	intron	N/A	NP_001341853.1	X5D3F6
IRF1	NM_001354925.1		c.545-7T>C	splice_region 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.545-7T>C	splice_region intron	N/A	ENSP00000245414.4	P10914
ENSG00000283782	ENST00000638452.2	TSL:5	c.-169+36691A>G	intron	N/A	ENSP00000492349.2	A0A1W2PQ90
CARINH	ENST00000612967.2	TSL:1	n.469A>G	non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57575

AN:

151940

Hom.:

11291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.361

GnomAD2 exomes

AF:

0.348

AC:

86678

AN:

248886

AF XY:

0.348

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:

0.325

Gnomad NFE exome

AF:

0.330

Gnomad OTH exome

AF:

0.357

GnomAD4 exome

AF:

0.341

AC:

497694

AN:

1458306

Hom.:

86080

Cov.:

AF XY:

0.342

AC XY:

248129

AN XY:

725544

show subpopulations

African (AFR)

AF:

0.491

AC:

16445

AN:

33466

American (AMR)

AF:

0.331

AC:

14820

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

8250

AN:

26124

East Asian (EAS)

AF:

0.331

AC:

13119

AN:

39682

South Asian (SAS)

AF:

0.387

AC:

33370

AN:

86226

European-Finnish (FIN)

AF:

0.327

AC:

16499

AN:

50496

Middle Eastern (MID)

AF:

0.404

AC:

2328

AN:

5764

European-Non Finnish (NFE)

AF:

0.335

AC:

371794

AN:

1111478

Other (OTH)

AF:

0.349

AC:

21069

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

18791

37582

56374

75165

93956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12244

24488

36732

48976

61220

<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:

57632

AN:

152058

Hom.:

11305

Cov.:

AF XY:

0.378

AC XY:

28112

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.487

AC:

20186

AN:

41442

American (AMR)

AF:

0.343

AC:

5252

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1122

AN:

3470

East Asian (EAS)

AF:

0.361

AC:

1862

AN:

5156

South Asian (SAS)

AF:

0.410

AC:

1976

AN:

4820

European-Finnish (FIN)

AF:

0.329

AC:

3483

AN:

10578

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22639

AN:

67972

Other (OTH)

AF:

0.361

AC:

761

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1831

3662

5492

7323

9154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<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:

0.348

Hom.:

2795

Bravo

AF:

0.382

Asia WGS

AF:

0.377

AC:

1312

AN:

3478

EpiCase

AF:

0.329

EpiControl

AF:

0.325

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

-0.86

CADD

Benign

5.7

(source)

DANN

Benign

0.45

PhyloP100

0.13

PromoterAI

-0.013

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

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