rs6975315

Variant names:

• chr7-128942431-G-A
• rs6975315
• NM_001098629.3:c.195+155G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098629.3(IRF5):​c.195+155G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 151,766 control chromosomes in the GnomAD database, including 298 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.046 (298 hom., cov: 32)
• Consequence: IRF5 NM_001098629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.195+155G>A		intron_variant	Intron 2 of 8	ENST00000357234.10	NP_001092099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10	c.195+155G>A		intron_variant	Intron 2 of 8	1	NM_001098629.3	ENSP00000349770.5

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 6986 AN: 151676 Hom.: 298 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.00400

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.0230

Gnomad OTH AF: 0.0394

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0461 AC: 6995 AN: 151766 Hom.: 298 Cov.: 32 AF XY: 0.0449 AC XY: 3328 AN XY: 74152

African (AFR) AF: 0.112 AC: 4622 AN: 41308

American (AMR) AF: 0.0279 AC: 426 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.0442 AC: 212 AN: 4800

European-Finnish (FIN) AF: 0.00400 AC: 42 AN: 10492

Middle Eastern (MID) AF: 0.0138 AC: 4 AN: 290

European-Non Finnish (NFE) AF: 0.0230 AC: 1560 AN: 67962

Other (OTH) AF: 0.0390 AC: 82 AN: 2102

Alfa AF: 0.0272 Hom.: 104

Bravo AF: 0.0496

Asia WGS AF: 0.0230 AC: 82 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.21
DANN	Benign	0.71
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6975315; hg19: chr7-128582485;