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

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 links:

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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

Gnomad4 AFR exome

AF:

0.0189

AC:

456

AN:

24162

Gnomad4 AMR exome

AF:

0.191

AC:

4546

AN:

23764

Gnomad4 ASJ exome

AF:

0.113

AC:

2008

AN:

17842

Gnomad4 EAS exome

AF:

0.000253

AC:

AN:

35524

Gnomad4 SAS exome

AF:

0.157

AC:

9560

AN:

60908

Gnomad4 FIN exome

AF:

0.152

AC:

4881

AN:

32194

Gnomad4 NFE exome

AF:

0.109

AC:

88236

AN:

805970

Gnomad4 Remaining exome

AF:

0.108

AC:

4987

AN:

45968

Heterozygous variant carriers

5081

10163

15244

20326

25407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.0243

AC:

0.0242805

AN:

0.0242805

Gnomad4 AMR

AF:

0.139

AC:

0.138515

AN:

0.138515

Gnomad4 ASJ

AF:

0.114

AC:

0.114187

AN:

0.114187

Gnomad4 EAS

AF:

0.00193

AC:

0.00193125

AN:

0.00193125

Gnomad4 SAS

AF:

0.154

AC:

0.153543

AN:

0.153543

Gnomad4 FIN

AF:

0.145

AC:

0.145146

AN:

0.145146

Gnomad4 NFE

AF:

0.113

AC:

0.112545

AN:

0.112545

Gnomad4 OTH

AF:

0.102

AC:

0.101799

AN:

0.101799

Heterozygous variant carriers

639

1278

1918

2557

3196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

DANN

Benign

0.40

Mutation Taster

=100/0

polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over