rs60344245

chr7-128947297-CACTCTGCAGCCGCCCACTCTGCGGCCGCCT-Cchr7-128947297-CACTCTGCAGCCGCCCACTCTGCGGCCGCCT-CACTCTGCAGCCGCCCACTCTGCGGCCGCCTACTCTGCAGCCGCCCACTCTGCGGCCGCCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_001098629.3(IRF5):c.572_601del(p.Arg191_Leu200del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,594 control chromosomes in the GnomAD database, including 18,851 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (18851 hom., cov: 0)
  • Exomes 𝑓: 0.50 (180811 hom.)
  • Failed GnomAD Quality Control
• Consequence: IRF5 NM_001098629.3 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.736

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001098629.3.
• BP6: Variant 7-128947297-CACTCTGCAGCCGCCCACTCTGCGGCCGCCT-C is Benign according to our data. Variant chr7-128947297-CACTCTGCAGCCGCCCACTCTGCGGCCGCCT-C is described in ClinVar as [Benign]. Clinvar id is 768201.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF5	NM_001098629.3	c.572_601del	p.Arg191_Leu200del	inframe_deletion	6/9	ENST00000357234.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF5	ENST00000357234.10	c.572_601del	p.Arg191_Leu200del	inframe_deletion	6/9	1	NM_001098629.3

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75054 AN: 151476 Hom.: 18838 Cov.: 0

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.500

GnomAD3 exomes AF: 0.463 AC: 108068 AN: 233398 Hom.: 25427 AF XY: 0.467 AC XY: 59680 AN XY: 127798

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.300

Gnomad ASJ exome AF: 0.585

Gnomad EAS exome AF: 0.485

Gnomad SAS exome AF: 0.461

Gnomad FIN exome AF: 0.470

Gnomad NFE exome AF: 0.492

Gnomad OTH exome AF: 0.465

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.496 AC: 720257 AN: 1451580 Hom.: 180811 AF XY: 0.496 AC XY: 358146 AN XY: 721776

Gnomad4 AFR exome AF: 0.529

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.595

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.476

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.499

GnomAD4 genome AF: 0.495 AC: 75108 AN: 151594 Hom.: 18851 Cov.: 0 AF XY: 0.490 AC XY: 36268 AN XY: 74040

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.498

Alfa AF: 0.498 Hom.: 3203

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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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;