rs2004640

Positions:

• chr7-128938247-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098629.3(IRF5):​c.-12+198T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,736 control chromosomes in the GnomAD database, including 21,339 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 0.53 (21302 hom., cov: 32)
  • Exomes 𝑓: 0.56 (37 hom.)
• Consequence: IRF5 NM_001098629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.802

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.-12+198T>G		intron_variant		ENST00000357234.10	NP_001092099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10	c.-12+198T>G		intron_variant		1	NM_001098629.3	ENSP00000349770

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79628 AN: 151418 Hom.: 21275 Cov.: 32

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.491

GnomAD4 exome AF: 0.559 AC: 113 AN: 202 Hom.: 37 Cov.: 0 AF XY: 0.549 AC XY: 89 AN XY: 162

Gnomad4 AFR exome AF: 0.750

Gnomad4 EAS exome AF: 0.833

Gnomad4 SAS exome AF: 0.750

Gnomad4 NFE exome AF: 0.547

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.526 AC: 79705 AN: 151534 Hom.: 21302 Cov.: 32 AF XY: 0.529 AC XY: 39171 AN XY: 74052

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.494

Alfa AF: 0.377 Hom.: 1334

Bravo AF: 0.531

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.9

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2004640; hg19: chr7-128578301;