rs3834330

Variant names:

• chr7-128937265-GGT-G
• rs3834330
• XM_011516160.2:c.-575_-574delTG

Your query was ambiguous. Multiple possible variants found:

• chr7-128937265-GGT-G
• chr7-128937265-GGT-GGTGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The XM_011516160.2(IRF5):​c.-575_-574delTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,236 control chromosomes in the GnomAD database, including 919 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (919 hom., cov: 31)
• Consequence: IRF5 XM_011516160.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 1 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	XM_011516160.2	c.-575_-574delTG		5_prime_UTR_variant	Exon 1 of 9		XP_011514462.1
IRF5	XM_047420338.1	c.-575_-574delTG		5_prime_UTR_variant	Exon 1 of 9		XP_047276294.1
IRF5	NM_001347928.2	c.-12+6_-12+7delTG		splice_region_variant, intron_variant	Intron 1 of 8		NP_001334857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000652525.1	c.-440_-439delGT		upstream_gene_variant				ENSP00000498293.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16468 AN: 152118 Hom.: 916 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0683

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0757

Gnomad SAS AF: 0.0946

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0966

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

GnomAD4 genome AF: 0.108 AC: 16487 AN: 152236 Hom.: 919 Cov.: 31 AF XY: 0.109 AC XY: 8098 AN XY: 74430

African (AFR) AF: 0.110 AC: 4548 AN: 41526

American (AMR) AF: 0.0681 AC: 1043 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3468

East Asian (EAS) AF: 0.0757 AC: 393 AN: 5192

South Asian (SAS) AF: 0.0947 AC: 457 AN: 4826

European-Finnish (FIN) AF: 0.124 AC: 1312 AN: 10582

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8000 AN: 68014

Other (OTH) AF: 0.0951 AC: 201 AN: 2114

Alfa AF: 0.116 Hom.: 122

Bravo AF: 0.103

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0

Splicing

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

Other links and lift over

dbSNP: rs3834330; hg19: chr7-128577319;