Genetic Variant NM_001347928.2:c.-12+608_-12+612dupGGGGC (chr7-128937860-C-CGCGGG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001347928.2(IRF5):c.-12+608_-12+612dupGGGGC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.37 ( 11067 hom., cov: 0)

Exomes 𝑓: 0.12 ( 1 hom. )

Consequence

IRF5
NM_001347928.2 intron

Scores

Not classified

Clinical Significance

risk factor no assertion criteria provided O:2

Conservation

PhyloP100: 0.213

Publications

8 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3 link	c.-201_-200insGCGGG		upstream_gene_variant		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.-201_-200insGCGGG		upstream_gene_variant		1	NM_001098629.3	ENSP00000349770.5		Q13568-2

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

55249

AN:

149364

Hom.:

11074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.452

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.521

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.387

Gnomad FIN

AF:

0.383

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.442

Gnomad OTH

AF:

0.409

GnomAD4 exome

AF:

0.117

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0946

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.132

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.370

AC:

55242

AN:

149474

Hom.:

11067

Cov.:

AF XY:

0.364

AC XY:

26566

AN XY:

72896

show subpopulations

African (AFR)

AF:

0.249

AC:

10198

AN:

41014

American (AMR)

AF:

0.400

AC:

6022

AN:

15058

Ashkenazi Jewish (ASJ)

AF:

0.521

AC:

1789

AN:

3436

East Asian (EAS)

AF:

0.121

AC:

613

AN:

5080

South Asian (SAS)

AF:

0.387

AC:

1837

AN:

4748

European-Finnish (FIN)

AF:

0.383

AC:

3845

AN:

10030

Middle Eastern (MID)

AF:

0.490

AC:

142

AN:

290

European-Non Finnish (NFE)

AF:

0.442

AC:

29553

AN:

66860

Other (OTH)

AF:

0.407

AC:

842

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

1459

2918

4378

5837

7296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.152

Hom.:

379

ClinVar

Significance: risk factor

Submissions summary: Other:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Inflammatory bowel disease 14, susceptibility to

Other:1

Mar 15, 2008

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Systemic lupus erythematosus, susceptibility to, 10

Other:1

Mar 15, 2008

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

PhyloP100

0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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NM_001347928.2:c.-12+608_-12+612dupGGGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over