Genetic Variant IRF5:p.Arg191_Leu200dup (chr7-128947297-C-CACTCTGCAGCCGCCCACTCTGCGGCCGCCT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001098629.3(IRF5):c.572_601dupGGCCGCCTACTCTGCAGCCGCCCACTCTGC(p.Arg191_Leu200dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

IRF5
NM_001098629.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0170

Publications

11 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: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001098629.3.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098629.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IRF5	NM_001098629.3	MANE Select	c.572_601dupGGCCGCCTACTCTGCAGCCGCCCACTCTGC	p.Arg191_Leu200dup	disruptive_inframe_insertion	Exon 6 of 9	NP_001092099.1
IRF5	NM_001347928.2		c.572_601dupGGCCGCCTACTCTGCAGCCGCCCACTCTGC	p.Arg191_Leu200dup	disruptive_inframe_insertion	Exon 6 of 9	NP_001334857.1
IRF5	NM_001364314.2		c.572_601dupGGCCGCCTACTCTGCAGCCGCCCACTCTGC	p.Arg191_Leu200dup	disruptive_inframe_insertion	Exon 6 of 9	NP_001351243.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IRF5	ENST00000357234.10	TSL:1 MANE Select	c.572_601dupGGCCGCCTACTCTGCAGCCGCCCACTCTGC	p.Arg191_Leu200dup	disruptive_inframe_insertion	Exon 6 of 9	ENSP00000349770.5
IRF5	ENST00000402030.6	TSL:1	c.524_553dupGGCCGCCTACTCTGCAGCCGCCCACTCTGC	p.Arg175_Leu184dup	disruptive_inframe_insertion	Exon 6 of 9	ENSP00000385352.2
IRF5	ENST00000477535.5	TSL:1	c.481+264_481+293dupGGCCGCCTACTCTGCAGCCGCCCACTCTGC		intron	N/A	ENSP00000419950.1

Frequencies

GnomAD3 genomes

AF:

0.0000725

AC:

AN:

151754

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000428

AC:

AN:

233398

AF XY:

0.0000235

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000894

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000570

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000195

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.0000405

AC:

AN:

1456740

Hom.:

Cov.:

AF XY:

0.0000511

AC XY:

AN XY:

724282

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33410

American (AMR)

AF:

0.0000901

AC:

AN:

44374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26020

East Asian (EAS)

AF:

0.000126

AC:

AN:

39576

South Asian (SAS)

AF:

0.000361

AC:

AN:

85754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1109932

Other (OTH)

AF:

0.0000832

AC:

AN:

60132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000724

AC:

AN:

151874

Hom.:

Cov.:

AF XY:

0.0000944

AC XY:

AN XY:

74190

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41400

American (AMR)

AF:

0.000393

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000388

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67898

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.017

Mutation Taster

=71/29

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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7-128947297-CACTCTGCAGCCGCCCACTCTGCGGCCGCCT-CACTCTGCAGCCGCCCACTCTGCGGCCGCCTACTCTGCAGCCGCCCACTCTGCGGCCGCCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over