7-128945322-A-T

Variant names:

• chr7-128945322-A-T
• rs1874327
• NM_001098629.3:c.196-523A>T

Variant summary

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

The NM_001098629.3(IRF5):​c.196-523A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,006 control chromosomes in the GnomAD database, including 31,243 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 0.64 (31243 hom., cov: 31)
• Consequence: IRF5 NM_001098629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• 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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.196-523A>T		intron_variant	Intron 2 of 8	ENST00000357234.10	NP_001092099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10	c.196-523A>T		intron_variant	Intron 2 of 8	1	NM_001098629.3	ENSP00000349770.5

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96899 AN: 151888 Hom.: 31216 Cov.: 31

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.638 AC: 96970 AN: 152006 Hom.: 31243 Cov.: 31 AF XY: 0.639 AC XY: 47480 AN XY: 74336

African (AFR) AF: 0.594 AC: 24605 AN: 41412

American (AMR) AF: 0.564 AC: 8612 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2620 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2885 AN: 5170

South Asian (SAS) AF: 0.690 AC: 3323 AN: 4816

European-Finnish (FIN) AF: 0.735 AC: 7771 AN: 10576

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 44972 AN: 67968

Other (OTH) AF: 0.647 AC: 1366 AN: 2112

Alfa AF: 0.643 Hom.: 3757

Bravo AF: 0.624

Asia WGS AF: 0.625 AC: 2175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.1
DANN	Benign	0.93
PhyloP100		-1.9
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: rs1874327; hg19: chr7-128585376;