Genetic Variant ENST00000493208.1:n.900T>G (chr5-132488794-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000493208.1(IRF1):n.900T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 153,290 control chromosomes in the GnomAD database, including 11,359 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 ( 11308 hom., cov: 32)

Exomes 𝑓: 0.27 ( 51 hom. )

Consequence

IRF1
ENST00000493208.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.230

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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.87+598T>G		intron_variant	Intron 2 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.87+598T>G		intron_variant	Intron 2 of 9	1	NM_002198.3	ENSP00000245414.4		P10914
ENSG00000283782	ENST00000638452.2 link	c.-169+39105A>C		intron_variant	Intron 3 of 26	5		ENSP00000492349.2		A0A1W2PQ90

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57608

AN:

151930

Hom.:

11294

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.330

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.360

GnomAD4 exome

AF:

0.269

AC:

334

AN:

1242

Hom.:

Cov.:

AF XY:

0.279

AC XY:

179

AN XY:

642

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.216

AC:

AN:

222

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.214

AC:

AN:

South Asian (SAS)

AF:

0.328

AC:

AN:

134

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.272

AC:

224

AN:

824

Other (OTH)

AF:

0.306

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

57665

AN:

152048

Hom.:

11308

Cov.:

AF XY:

0.378

AC XY:

28123

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.487

AC:

20197

AN:

41470

American (AMR)

AF:

0.345

AC:

5270

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1121

AN:

3470

East Asian (EAS)

AF:

0.360

AC:

1861

AN:

5164

South Asian (SAS)

AF:

0.409

AC:

1973

AN:

4820

European-Finnish (FIN)

AF:

0.330

AC:

3485

AN:

10570

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22650

AN:

67968

Other (OTH)

AF:

0.360

AC:

760

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1822

3644

5466

7288

9110

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:

0.359

Hom.:

3850

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

-0.91

CADD

Benign

5.2

(source)

DANN

Benign

0.49

PhyloP100

-0.23

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over