7-128947297-CACTCTGCAGCCGCCCACTCTGCGGCCGCCT-CACTCTGCAGCCGCCCACTCTGCGGCCGCCTACTCTGCAGCCGCCCACTCTGCGGCCGCCT

Position:

• chr7-128947297-CACTCTGCAGCCGCCCACTCTGCGGCCGCCT-CACTCTGCAGCCGCCCACTCTGCGGCCGCCTACTCTGCAGCCGCCCACTCTGCGGCCGCCT

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001098629.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.572_601dupGGCCGCCTACTCTGCAGCCGCCCACTCTGC	p.Arg191_Leu200dup	disruptive_inframe_insertion	6/9	ENST00000357234.10	NP_001092099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10	c.572_601dupGGCCGCCTACTCTGCAGCCGCCCACTCTGC	p.Arg191_Leu200dup	disruptive_inframe_insertion	6/9	1	NM_001098629.3	ENSP00000349770.5

Frequencies

GnomAD3 genomes AF: 0.0000725 AC: 11 AN: 151754 Hom.: 0 Cov.: 0

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

GnomAD3 exomes AF: 0.0000428 AC: 10 AN: 233398 Hom.: 0 AF XY: 0.0000235 AC XY: 3 AN XY: 127798

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 SAS exome AF: 0.000101

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000195

Gnomad OTH exome AF: 0.000174

GnomAD4 exome AF: 0.0000405 AC: 59 AN: 1456740 Hom.: 0 Cov.: 0 AF XY: 0.0000511 AC XY: 37 AN XY: 724282

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000901

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.000361

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.0000832

GnomAD4 genome AF: 0.0000724 AC: 11 AN: 151874 Hom.: 0 Cov.: 0 AF XY: 0.0000944 AC XY: 7 AN XY: 74190

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs60344245; hg19: chr7-128587351;