rs6953165

Positions:

• chr7-128938156-C-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+107C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0524 in 152,216 control chromosomes in the GnomAD database, including 251 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 0.052 (250 hom., cov: 32)
  • Exomes 𝑓: 0.063 (1 hom.)
• Consequence: IRF5 NM_001098629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.27

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.-12+107C>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+107C>G		intron_variant		1	NM_001098629.3	ENSP00000349770

Frequencies

GnomAD3 genomes AF: 0.0524 AC: 7973 AN: 152038 Hom.: 249 Cov.: 32

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.0891

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0490

Gnomad OTH AF: 0.0458

GnomAD4 exome AF: 0.0625 AC: 4 AN: 64 Hom.: 1 Cov.: 0 AF XY: 0.0556 AC XY: 3 AN XY: 54

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.333

Gnomad4 NFE exome AF: 0.0357

GnomAD4 genome AF: 0.0524 AC: 7971 AN: 152152 Hom.: 250 Cov.: 32 AF XY: 0.0554 AC XY: 4124 AN XY: 74380

Gnomad4 AFR AF: 0.0426

Gnomad4 AMR AF: 0.0368

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.0890

Gnomad4 SAS AF: 0.0795

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0490

Gnomad4 OTH AF: 0.0454

Alfa AF: 0.0487 Hom.: 26

Bravo AF: 0.0454

Asia WGS AF: 0.101 AC: 351 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs6953165; hg19: chr7-128578210;