Genetic Variant IRF5:c.195+10G>A (chr7-128942286-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001098629.3(IRF5):c.195+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,603,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

IRF5
NM_001098629.3 intron

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.215

Publications

0 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 7-128942286-G-A is Benign according to our data. Variant chr7-128942286-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3051361.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3 link	c.195+10G>A		intron_variant	Intron 2 of 8	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.195+10G>A		intron_variant	Intron 2 of 8	1	NM_001098629.3	ENSP00000349770.5		Q13568-2

Frequencies

GnomAD3 genomes

AF:

0.00119

AC:

181

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00396

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000371

AC:

AN:

242316

AF XY:

0.000313

show subpopulations

Gnomad AFR exome

AF:

0.00468

Gnomad AMR exome

AF:

0.000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000461

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000136

AC:

198

AN:

1450808

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

720478

show subpopulations

African (AFR)

AF:

0.00422

AC:

140

AN:

33196

American (AMR)

AF:

0.000227

AC:

AN:

44056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25660

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39324

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85426

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53084

Middle Eastern (MID)

AF:

0.000185

AC:

AN:

5394

European-Non Finnish (NFE)

AF:

0.0000281

AC:

AN:

1104846

Other (OTH)

AF:

0.000234

AC:

AN:

59822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00119

AC:

181

AN:

152294

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00395

AC:

164

AN:

41556

American (AMR)

AF:

0.000588

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68024

Other (OTH)

AF:

0.000946

AC:

AN:

2114

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

Alfa

AF:

0.000580

Hom.:

Bravo

AF:

0.00149

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IRF5-related disorder

Benign:1

Mar 22, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.2

(source)

DANN

Benign

0.40

PhyloP100

0.21

Mutation Taster

=100/0

polymorphism

(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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7-128942286-G-A

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