chr7-128935969-G-A

Variant names:

• chr7-128935969-G-A
• rs3757388
• ENST00000898739.1:c.-12+2371G>A

Variant summary

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

The ENST00000898739.1(IRF5):​c.-12+2371G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,874 control chromosomes in the GnomAD database, including 23,887 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 0.55 (23887 hom., cov: 31)
• Consequence: IRF5 ENST00000898739.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF5	ENST00000898739.1		c.-12+2371G>A		intron	N/A	ENSP00000568798.1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83258 AN: 151756 Hom.: 23882 Cov.: 31

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.548 AC: 83292 AN: 151874 Hom.: 23887 Cov.: 31 AF XY: 0.547 AC XY: 40606 AN XY: 74184

African (AFR) AF: 0.404 AC: 16720 AN: 41404

American (AMR) AF: 0.515 AC: 7857 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2548 AN: 3470

East Asian (EAS) AF: 0.357 AC: 1846 AN: 5164

South Asian (SAS) AF: 0.609 AC: 2922 AN: 4800

European-Finnish (FIN) AF: 0.643 AC: 6766 AN: 10522

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42652 AN: 67942

Other (OTH) AF: 0.580 AC: 1226 AN: 2114

Alfa AF: 0.582 Hom.: 3311

Bravo AF: 0.530

Asia WGS AF: 0.469 AC: 1633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.59
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs3757388; hg19: chr7-128576023;