chr7-128935170-C-T

Variant names:

• chr7-128935170-C-T
• rs1874330
• ENST00000898739.1:c.-12+1572C>T

Variant summary

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

The ENST00000898739.1(IRF5):​c.-12+1572C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,006 control chromosomes in the GnomAD database, including 37,782 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 0.68 (37782 hom., cov: 31)
• Consequence: IRF5 ENST00000898739.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.702
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000898739.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF5	ENST00000898739.1		c.-12+1572C>T		intron	N/A	ENSP00000568798.1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103719 AN: 151890 Hom.: 37791 Cov.: 31

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.682 AC: 103733 AN: 152006 Hom.: 37782 Cov.: 31 AF XY: 0.681 AC XY: 50630 AN XY: 74304

African (AFR) AF: 0.460 AC: 19070 AN: 41428

American (AMR) AF: 0.619 AC: 9455 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.861 AC: 2986 AN: 3470

East Asian (EAS) AF: 0.366 AC: 1883 AN: 5140

South Asian (SAS) AF: 0.753 AC: 3624 AN: 4812

European-Finnish (FIN) AF: 0.846 AC: 8979 AN: 10608

Middle Eastern (MID) AF: 0.829 AC: 242 AN: 292

European-Non Finnish (NFE) AF: 0.812 AC: 55206 AN: 67956

Other (OTH) AF: 0.702 AC: 1481 AN: 2110

Alfa AF: 0.736 Hom.: 5069

Bravo AF: 0.652

Asia WGS AF: 0.552 AC: 1919 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.65
DANN	Benign	0.32
PhyloP100		-0.70

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1874330;

hg19: chr7-128575224;