Genetic Variant IRF5:p.Pro192Pro (chr7-128947324-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001098629.3(IRF5):c.576G>A(p.Pro192Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0017 ( 4 hom. )

Consequence

IRF5
NM_001098629.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0640

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: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.013).

BP6

Variant 7-128947324-G-A is Benign according to our data. Variant chr7-128947324-G-A is described in ClinVar as [Benign]. Clinvar id is 720376.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0121 (489/40460) while in subpopulation AFR AF = 0.048 (467/9734). AF 95% confidence interval is 0.0444. There are 1 homozygotes in GnomAd4. There are 241 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3 link	c.576G>A	p.Pro192Pro	synonymous_variant	Exon 6 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.576G>A	p.Pro192Pro	synonymous_variant	Exon 6 of 9	1	NM_001098629.3	ENSP00000349770.5		Q13568-2

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

477

AN:

40414

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00237

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00136

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000229

Gnomad OTH

AF:

0.00368

GnomAD2 exomes

AF:

0.000927

AC:

214

AN:

230728

AF XY:

0.000703

show subpopulations

Gnomad AFR exome

AF:

0.0122

Gnomad AMR exome

AF:

0.000721

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.000879

GnomAD4 exome

AF:

0.00173

AC:

647

AN:

374292

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

293

AN XY:

185900

show subpopulations

African (AFR)

AF:

0.0493

AC:

392

AN:

7958

American (AMR)

AF:

0.00161

AC:

AN:

21120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4336

East Asian (EAS)

AF:

0.00

AC:

AN:

10610

South Asian (SAS)

AF:

0.000157

AC:

AN:

25538

European-Finnish (FIN)

AF:

0.0000709

AC:

AN:

14112

Middle Eastern (MID)

AF:

0.0125

AC:

AN:

1516

European-Non Finnish (NFE)

AF:

0.000500

AC:

137

AN:

273730

Other (OTH)

AF:

0.00390

AC:

AN:

15372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.541

Heterozygous variant carriers

126

157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0121

AC:

489

AN:

40460

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

241

AN XY:

20246

show subpopulations

African (AFR)

AF:

0.0480

AC:

467

AN:

9734

American (AMR)

AF:

0.00236

AC:

AN:

5930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

586

East Asian (EAS)

AF:

0.00

AC:

AN:

1514

South Asian (SAS)

AF:

0.00136

AC:

AN:

1470

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000229

AC:

AN:

17458

Other (OTH)

AF:

0.00362

AC:

AN:

552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00284

Hom.:

Bravo

AF:

0.00365

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.8

(source)

DANN

Benign

0.73

PhyloP100

0.064

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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chr7-128947324-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