rs2070197

Positions:

• chr7-128948946-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000357234.10(IRF5):​c.*128T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,201,678 control chromosomes in the GnomAD database, including 8,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.090 (862 hom., cov: 33)
  • Exomes 𝑓: 0.11 (7225 hom.)
• Consequence: IRF5 ENST00000357234.10 3_prime_UTR
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.862

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.*128T>C		3_prime_UTR_variant	9/9	ENST00000357234.10	NP_001092099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10	c.*128T>C		3_prime_UTR_variant	9/9	1	NM_001098629.3	ENSP00000349770

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13755 AN: 152100 Hom.: 865 Cov.: 33

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.110 AC: 115067 AN: 1049460 Hom.: 7225 Cov.: 14 AF XY: 0.111 AC XY: 57904 AN XY: 522450

Gnomad4 AFR exome AF: 0.0189

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.000253

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.0903 AC: 13749 AN: 152218 Hom.: 862 Cov.: 33 AF XY: 0.0930 AC XY: 6922 AN XY: 74438

Gnomad4 AFR AF: 0.0243

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.102

Alfa AF: 0.101 Hom.: 138

Bravo AF: 0.0870

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Systemic lupus erythematosus, association with susceptibility to, 10 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2070197; hg19: chr7-128589000; COSMIC: COSV50857256; COSMIC: COSV50857256;