Genetic Variant IRF5:c.*128T>C (chr7-128948946-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001098629.3(IRF5):c.*128T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,201,678 control chromosomes in the GnomAD database, including 8,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.090 ( 862 hom., cov: 33)

Exomes 𝑓: 0.11 ( 7225 hom. )

Consequence

IRF5
NM_001098629.3 3_prime_UTR

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: -0.862

Publications

78 publications found

Variant links:

Genes affected

IRF5 (HGNC:6120): (interferon regulatory factor 5) This gene encodes a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats. Alternative promoter use and alternative splicing result in multiple transcript variants, and a 30-nt indel polymorphism (SNP rs60344245) can result in loss of a 10-aa segment. [provided by RefSeq, Dec 2016]

IRF5 Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

IRF5 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=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3 link	c.*128T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000357234.10	NP_001092099.1	Q13568-2B7Z1M2C9JAU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10 link	c.*128T>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_001098629.3	ENSP00000349770.5		Q13568-2

Frequencies

GnomAD3 genomes

AF:

0.0904

AC:

13755

AN:

152100

Hom.:

865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.103

GnomAD4 exome

AF:

0.110

AC:

115067

AN:

1049460

Hom.:

7225

Cov.:

AF XY:

0.111

AC XY:

57904

AN XY:

522450

show subpopulations

African (AFR)

AF:

0.0189

AC:

456

AN:

24162

American (AMR)

AF:

0.191

AC:

4546

AN:

23764

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

2008

AN:

17842

East Asian (EAS)

AF:

0.000253

AC:

AN:

35524

South Asian (SAS)

AF:

0.157

AC:

9560

AN:

60908

European-Finnish (FIN)

AF:

0.152

AC:

4881

AN:

32194

Middle Eastern (MID)

AF:

0.123

AC:

384

AN:

3128

European-Non Finnish (NFE)

AF:

0.109

AC:

88236

AN:

805970

Other (OTH)

AF:

0.108

AC:

4987

AN:

45968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5081

10163

15244

20326

25407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2938

5876

8814

11752

14690

<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:

0.0903

AC:

13749

AN:

152218

Hom.:

862

Cov.:

AF XY:

0.0930

AC XY:

6922

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0243

AC:

1009

AN:

41556

American (AMR)

AF:

0.139

AC:

2119

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

396

AN:

3468

East Asian (EAS)

AF:

0.00193

AC:

AN:

5178

South Asian (SAS)

AF:

0.154

AC:

741

AN:

4826

European-Finnish (FIN)

AF:

0.145

AC:

1540

AN:

10610

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.113

AC:

7649

AN:

67964

Other (OTH)

AF:

0.102

AC:

215

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

639

1278

1918

2557

3196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.0983

Hom.:

138

Bravo

AF:

0.0870

Asia WGS

AF:

0.0580

AC:

202

AN:

3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SYSTEMIC LUPUS ERYTHEMATOSUS, ASSOCIATION WITH SUSCEPTIBILITY TO, 10

Other:1

Jul 01, 2007

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.8

(source)

DANN

Benign

0.40

PhyloP100

-0.86

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over