chr7-128933940-C-T

Variant names:

• chr7-128933940-C-T
• rs7801838
• ENST00000898739.1:c.-12+342C>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+342C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,128 control chromosomes in the GnomAD database, including 4,608 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 0.22 (4608 hom., cov: 33)
• Consequence: IRF5 ENST00000898739.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.526
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 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+342C>T		intron	N/A	ENSP00000568798.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33887 AN: 152010 Hom.: 4613 Cov.: 33

Gnomad AFR AF: 0.0911

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0845

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.223 AC: 33870 AN: 152128 Hom.: 4608 Cov.: 33 AF XY: 0.223 AC XY: 16587 AN XY: 74362

African (AFR) AF: 0.0910 AC: 3778 AN: 41516

American (AMR) AF: 0.168 AC: 2566 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3470

East Asian (EAS) AF: 0.0845 AC: 438 AN: 5186

South Asian (SAS) AF: 0.241 AC: 1161 AN: 4808

European-Finnish (FIN) AF: 0.318 AC: 3363 AN: 10566

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20861 AN: 67974

Other (OTH) AF: 0.202 AC: 426 AN: 2114

Alfa AF: 0.262 Hom.: 718

Bravo AF: 0.203

Asia WGS AF: 0.156 AC: 541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.65
PhyloP100		0.53

Splicing

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

Other links and lift over

dbSNP: rs7801838; hg19: chr7-128573994;