7-128939366-T-C

Variant names:

• chr7-128939366-T-C
• rs752637
• NM_001098629.3:c.-12+1317T>C

Variant summary

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

The NM_001098629.3(IRF5):​c.-12+1317T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,906 control chromosomes in the GnomAD database, including 26,127 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 0.58 (26127 hom., cov: 32)
• Consequence: IRF5 NM_001098629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 38 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.-12+1317T>C		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.-12+1317T>C		intron_variant	Intron 1 of 8	1	NM_001098629.3	ENSP00000349770.5

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88162 AN: 151788 Hom.: 26112 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.581 AC: 88212 AN: 151906 Hom.: 26127 Cov.: 32 AF XY: 0.578 AC XY: 42916 AN XY: 74222

African (AFR) AF: 0.522 AC: 21618 AN: 41432

American (AMR) AF: 0.525 AC: 8021 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2505 AN: 3470

East Asian (EAS) AF: 0.361 AC: 1851 AN: 5132

South Asian (SAS) AF: 0.604 AC: 2912 AN: 4820

European-Finnish (FIN) AF: 0.645 AC: 6804 AN: 10554

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42485 AN: 67914

Other (OTH) AF: 0.599 AC: 1261 AN: 2104

Alfa AF: 0.614 Hom.: 24611

Bravo AF: 0.569

Asia WGS AF: 0.480 AC: 1672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.94
DANN	Benign	0.60
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs752637; hg19: chr7-128579420;