7-128937860-C-CGCGGG

Position:

• chr7-128937860-C-CGCGGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001347928.2(IRF5):​c.-12+608_-12+612dup 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
• Clinical Significance: risk factor no assertion criteria provided O:2
• Conservation: PhyloP100: 0.213

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.

• 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/exons	MANE	UniProt
IRF5	NM_001347928.2	c.-12+608_-12+612dup		intron_variant
IRF5	XM_011516160.2	c.-12+39_-12+43dup		intron_variant
IRF5	XM_047420338.1	c.-12+39_-12+43dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF5	ENST00000489702.6	c.-12+39_-12+43dup		intron_variant		5
IRF5	ENST00000652525.1	c.-12+179_-12+183dup		intron_variant
IRF5	ENST00000700148.1	n.52+39_52+43dup		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.370 AC: 55249 AN: 149364 Hom.: 11074 Cov.: 0

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: 11 AN: 94 Hom.: 1 Cov.: 0 AF XY: 0.0946 AC XY: 7 AN XY: 74

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.370 AC: 55242 AN: 149474 Hom.: 11067 Cov.: 0 AF XY: 0.364 AC XY: 26566 AN XY: 72896

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.407

ClinVar

Significance: risk factor

Submissions summary: Other:2

Revision: no assertion criteria provided

Submissions by phenotype

Inflammatory bowel disease 14, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 15, 2008

- -

Systemic lupus erythematosus, susceptibility to, 10 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 15, 2008

- -

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: rs77571059; hg19: chr7-128577914;