Genetic Variant ENST00000493208.1:n.34C>G (chr5-132490721-G-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.34C>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 0.253 in 152,228 control chromosomes in the GnomAD database, including 6,169 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 0.25 ( 6164 hom., cov: 33)

Exomes 𝑓: 0.30 ( 5 hom. )

Consequence

IRF1
ENST00000493208.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

Publications

15 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 Gene-Disease associations (from GenCC):

immunodeficiency 117
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

IRF1 links:

ENSG00000283782 (HGNC:):

ENSG00000283782 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=-0.94).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF1	NM_002198.3 link	c.-182C>G		5_prime_UTR_variant	Exon 1 of 10	ENST00000245414.9	NP_002189.1	P10914Q6FHN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9 link	c.-182C>G		5_prime_UTR_variant	Exon 1 of 10	1	NM_002198.3	ENSP00000245414.4		P10914
ENSG00000283782	ENST00000638452.2 link	c.-169+41032G>C		intron_variant	Intron 3 of 26	5		ENSP00000492349.2		A0A1W2PQ90

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38423

AN:

151990

Hom.:

6162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0916

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.00987

Gnomad SAS

AF:

0.0963

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.308

GnomAD4 exome

AF:

0.303

AC:

AN:

122

Hom.:

Cov.:

AF XY:

0.261

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.318

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.311

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.253

AC:

38431

AN:

152106

Hom.:

6164

Cov.:

AF XY:

0.242

AC XY:

18002

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0915

AC:

3801

AN:

41542

American (AMR)

AF:

0.277

AC:

4240

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

1148

AN:

3466

East Asian (EAS)

AF:

0.00990

AC:

AN:

5152

South Asian (SAS)

AF:

0.0964

AC:

465

AN:

4826

European-Finnish (FIN)

AF:

0.255

AC:

2704

AN:

10586

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.365

AC:

24797

AN:

67926

Other (OTH)

AF:

0.308

AC:

652

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1389

2778

4167

5556

6945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.290

Hom.:

951

Bravo

AF:

0.252

Asia WGS

AF:

0.0820

AC:

285

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

9.0

(source)

DANN

Benign

0.73

PhyloP100

1.5

PromoterAI

-0.0024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

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