rs12422022

Variant names:

• chr11-613192-A-G
• rs12422022
• NM_001572.5:c.1237+14T>C

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -0.621
• Publications: 11 publications found

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]

IRF7 Gene-Disease associations (from GenCC):

• immunodeficiency 39

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
IRF7	NM_001572.5	c.1237+14T>C		intron_variant	Intron 9 of 10	ENST00000525445.6	NP_001563.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF7	ENST00000525445.6	c.1237+14T>C		intron_variant	Intron 9 of 10	5	NM_001572.5	ENSP00000434009.2

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

GnomAD2 exomes AF: 0.248 AC: 57295 AN: 230658 AF XY: 0.238

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 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

African (AFR) AF: 0.522 AC: 16983 AN: 32562

American (AMR) AF: 0.316 AC: 13071 AN: 41388

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 8295 AN: 24862

East Asian (EAS) AF: 0.0228 AC: 898 AN: 39384

South Asian (SAS) AF: 0.142 AC: 12023 AN: 84578

European-Finnish (FIN) AF: 0.198 AC: 10182 AN: 51450

Middle Eastern (MID) AF: 0.304 AC: 1719 AN: 5652

European-Non Finnish (NFE) AF: 0.274 AC: 300484 AN: 1097620

Other (OTH) AF: 0.272 AC: 16069 AN: 59116

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

African (AFR) AF: 0.518 AC: 21519 AN: 41510

American (AMR) AF: 0.307 AC: 4695 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3470

East Asian (EAS) AF: 0.0255 AC: 132 AN: 5182

South Asian (SAS) AF: 0.127 AC: 615 AN: 4828

European-Finnish (FIN) AF: 0.185 AC: 1961 AN: 10604

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18335 AN: 67942

Other (OTH) AF: 0.330 AC: 698 AN: 2114

Alfa AF: 0.313 Hom.: 1496

Bravo AF: 0.345

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency 39 Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.32
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12422022; hg19: chr11-613192;