rs12422022

chr11-613192-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001572.5(IRF7):c.1237+14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,588,768 control chromosomes in the GnomAD database, including 63,222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9399 hom., cov: 32)
  • Exomes 𝑓: 0.26 (53823 hom.)
• Consequence: IRF7 NM_001572.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.621

Genes affected

IRF7 (HGNC:6122): (interferon regulatory factor 7) This gene encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. It has been shown to play a role in the transcriptional activation of virus-inducible cellular genes, including interferon beta chain genes. Inducible expression of IRF7 is largely restricted to lymphoid tissue. The encoded protein plays an important role in the innate immune response against DNA and RNA viruses. [provided by RefSeq, Jul 2021]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-613192-A-G is Benign according to our data. Variant chr11-613192-A-G is described in ClinVar as [Benign]. Clinvar id is 1166881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF7	NM_001572.5	c.1237+14T>C		intron_variant		ENST00000525445.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF7	ENST00000525445.6	c.1237+14T>C		intron_variant		5	NM_001572.5	P2

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49397 AN: 152038 Hom.: 9383 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.332

GnomAD3 exomes AF: 0.248 AC: 57295 AN: 230658 Hom.: 8369 AF XY: 0.238 AC XY: 30001 AN XY: 125872

Gnomad AFR exome AF: 0.513

Gnomad AMR exome AF: 0.318

Gnomad ASJ exome AF: 0.334

Gnomad EAS exome AF: 0.0277

Gnomad SAS exome AF: 0.139

Gnomad FIN exome AF: 0.186

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.258

GnomAD4 exome AF: 0.264 AC: 379724 AN: 1436612 Hom.: 53823 Cov.: 38 AF XY: 0.260 AC XY: 184920 AN XY: 712180

Gnomad4 AFR exome AF: 0.522

Gnomad4 AMR exome AF: 0.316

Gnomad4 ASJ exome AF: 0.334

Gnomad4 EAS exome AF: 0.0228

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.272

GnomAD4 genome AF: 0.325 AC: 49448 AN: 152156 Hom.: 9399 Cov.: 32 AF XY: 0.314 AC XY: 23370 AN XY: 74410

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.330

Alfa AF: 0.308 Hom.: 1416

Bravo AF: 0.345

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency 39 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 59% of patients studied by a panel of primary immunodeficiencies. Number of patients: 56. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.4
Dann	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs12422022; hg19: chr11-613192;