7-128940626-G-T

Position:

• chr7-128940626-G-T

Variant summary

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

The NM_001098629.3(IRF5):​c.-11-1445G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 153,516 control chromosomes in the GnomAD database, including 14,830 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 0.43 (14684 hom., cov: 34)
  • Exomes 𝑓: 0.46 (146 hom.)
• Consequence: IRF5 NM_001098629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.-11-1445G>T		intron_variant		ENST00000357234.10	NP_001092099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10	c.-11-1445G>T		intron_variant		1	NM_001098629.3	ENSP00000349770

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65234 AN: 152036 Hom.: 14681 Cov.: 34

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.456 AC: 624 AN: 1368 Hom.: 146 Cov.: 0 AF XY: 0.453 AC XY: 338 AN XY: 746

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.441

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.508

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.560

GnomAD4 genome AF: 0.429 AC: 65252 AN: 152148 Hom.: 14684 Cov.: 34 AF XY: 0.425 AC XY: 31572 AN XY: 74372

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.462

Alfa AF: 0.469 Hom.: 20699

Bravo AF: 0.421

Asia WGS AF: 0.294 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.49

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: rs3807306; hg19: chr7-128580680;