rs11246213

chr11-612967-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.1356+32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,605,328 control chromosomes in the GnomAD database, including 64,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9395 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54811 hom.)
• Consequence: IRF7 NM_001572.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.64

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=-0.97).
• BP6: Variant 11-612967-A-G is Benign according to our data. Variant chr11-612967-A-G is described in ClinVar as [Benign]. Clinvar id is 1185463.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.1356+32T>C		intron_variant		ENST00000525445.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF7	ENST00000525445.6	c.1356+32T>C		intron_variant		5	NM_001572.5	P2

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49370 AN: 151908 Hom.: 9379 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.0255

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: 0.254 AC: 63399 AN: 249288 Hom.: 9651 AF XY: 0.244 AC XY: 32903 AN XY: 134994

Gnomad AFR exome AF: 0.523

Gnomad AMR exome AF: 0.324

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.0283

Gnomad SAS exome AF: 0.140

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.268

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.265 AC: 385219 AN: 1453304 Hom.: 54811 Cov.: 31 AF XY: 0.260 AC XY: 188365 AN XY: 723276

Gnomad4 AFR exome AF: 0.522

Gnomad4 AMR exome AF: 0.321

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.0228

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.325 AC: 49421 AN: 152024 Hom.: 9395 Cov.: 32 AF XY: 0.314 AC XY: 23357 AN XY: 74326

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.330

Alfa AF: 0.289 Hom.: 6770

Bravo AF: 0.345

Asia WGS AF: 0.125 AC: 437 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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. -

Immunodeficiency 39 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.43
Dann	Benign	0.43

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: rs11246213; hg19: chr11-612967; COSMIC: COSV52762490; COSMIC: COSV52762490;