rs11761199

Variant names:

• chr7-128941781-A-G
• rs11761199
• NM_001098629.3:c.-11-290A>G

Variant summary

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

The NM_001098629.3(IRF5):​c.-11-290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,954 control chromosomes in the GnomAD database, including 11,593 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 0.37 (11593 hom., cov: 32)
• Consequence: IRF5 NM_001098629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566
• Publications: 27 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.-11-290A>G		intron_variant	Intron 1 of 8	ENST00000357234.10	NP_001092099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10	c.-11-290A>G		intron_variant	Intron 1 of 8	1	NM_001098629.3	ENSP00000349770.5

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56056 AN: 151836 Hom.: 11588 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.369 AC: 56075 AN: 151954 Hom.: 11593 Cov.: 32 AF XY: 0.371 AC XY: 27557 AN XY: 74278

African (AFR) AF: 0.177 AC: 7337 AN: 41450

American (AMR) AF: 0.400 AC: 6109 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1815 AN: 3472

East Asian (EAS) AF: 0.331 AC: 1702 AN: 5140

South Asian (SAS) AF: 0.468 AC: 2248 AN: 4802

European-Finnish (FIN) AF: 0.483 AC: 5109 AN: 10580

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30456 AN: 67936

Other (OTH) AF: 0.395 AC: 835 AN: 2112

Alfa AF: 0.423 Hom.: 18061

Bravo AF: 0.357

Asia WGS AF: 0.375 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.45
PhyloP100		-0.57
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: rs11761199; hg19: chr7-128581835;