chr7-128938253-C-G

Position:

• chr7-128938253-C-G

Variant summary

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

The NM_032643.5(IRF5):​c.-12+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 152,378 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.036 (284 hom., cov: 31)
  • Exomes 𝑓: 0.043 (0 hom.)
• Consequence: IRF5 NM_032643.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.-12+204C>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+204C>G		intron_variant		1	NM_001098629.3	ENSP00000349770.5

Frequencies

GnomAD3 genomes AF: 0.0361 AC: 5486 AN: 152098 Hom.: 285 Cov.: 31

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00544

Gnomad OTH AF: 0.0316

GnomAD4 exome AF: 0.0427 AC: 7 AN: 164 Hom.: 0 Cov.: 0 AF XY: 0.0431 AC XY: 5 AN XY: 116

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.250

Gnomad4 NFE exome AF: 0.0147

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.0361 AC: 5495 AN: 152214 Hom.: 284 Cov.: 31 AF XY: 0.0383 AC XY: 2848 AN XY: 74432

Gnomad4 AFR AF: 0.0682

Gnomad4 AMR AF: 0.0327

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.0713

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.00544

Gnomad4 OTH AF: 0.0332

Alfa AF: 0.0221 Hom.: 19

Bravo AF: 0.0407

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.69

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: rs41298401; hg19: chr7-128578307;