Genetic Variant IRF1:c.667+205G>T (chr5-132486046-C-A) – 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.667+205G>T 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 677,058 control chromosomes in the GnomAD database, including 41,450 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 ( 11245 hom., cov: 31)

Exomes 𝑓: 0.34 ( 30205 hom. )

Consequence

IRF1
NM_002198.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.420

Publications

7 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=-0.78).

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.667+205G>T		intron_variant	Intron 7 of 9	ENST00000245414.9	NP_002189.1	P10914Q6FHN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9 link	c.667+205G>T		intron_variant	Intron 7 of 9	1	NM_002198.3	ENSP00000245414.4		P10914
ENSG00000283782	ENST00000638452.2 link	c.-169+36357C>A		intron_variant	Intron 3 of 26	5		ENSP00000492349.2		A0A1W2PQ90

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57360

AN:

151632

Hom.:

11231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.486

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.360

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.328

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.360

GnomAD4 exome

AF:

0.335

AC:

176235

AN:

525308

Hom.:

30205

Cov.:

AF XY:

0.337

AC XY:

93312

AN XY:

276848

show subpopulations

African (AFR)

AF:

0.487

AC:

6946

AN:

14268

American (AMR)

AF:

0.328

AC:

7150

AN:

21774

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

4532

AN:

14354

East Asian (EAS)

AF:

0.325

AC:

10652

AN:

32746

South Asian (SAS)

AF:

0.382

AC:

19563

AN:

51242

European-Finnish (FIN)

AF:

0.327

AC:

10290

AN:

31470

Middle Eastern (MID)

AF:

0.393

AC:

1233

AN:

3138

European-Non Finnish (NFE)

AF:

0.323

AC:

106022

AN:

327794

Other (OTH)

AF:

0.345

AC:

9847

AN:

28522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

5711

11422

17133

22844

28555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1248

2496

3744

4992

6240

<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:

57417

AN:

151750

Hom.:

11245

Cov.:

AF XY:

0.377

AC XY:

27991

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.486

AC:

20099

AN:

41318

American (AMR)

AF:

0.342

AC:

5213

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1119

AN:

3466

East Asian (EAS)

AF:

0.359

AC:

1847

AN:

5146

South Asian (SAS)

AF:

0.409

AC:

1969

AN:

4814

European-Finnish (FIN)

AF:

0.328

AC:

3450

AN:

10530

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22611

AN:

67906

Other (OTH)

AF:

0.360

AC:

758

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1738

3476

5213

6951

8689

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:

0.221

Hom.:

485

Bravo

AF:

0.382

Asia WGS

AF:

0.377

AC:

1312

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

0.42

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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