11-613297-T-G

Position:

• chr11-613297-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001572.5(IRF7):​c.1146A>C​(p.Gly382Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,607,992 control chromosomes in the GnomAD database, including 64,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9387 hom., cov: 31)
  • Exomes 𝑓: 0.27 (54971 hom.)
• Consequence: IRF7 NM_001572.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: -1.78

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-613297-T-G is Benign according to our data. Variant chr11-613297-T-G is described in ClinVar as [Benign]. Clinvar id is 1170387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.78 with no splicing effect.
• 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	Protein	UniProt
IRF7	NM_001572.5	c.1146A>C	p.Gly382Gly	synonymous_variant	9/11	ENST00000525445.6	NP_001563.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF7	ENST00000525445.6	c.1146A>C	p.Gly382Gly	synonymous_variant	9/11	5	NM_001572.5	ENSP00000434009.2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49340 AN: 151520 Hom.: 9371 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.333

GnomAD3 exomes AF: 0.252 AC: 60036 AN: 237930 Hom.: 8939 AF XY: 0.243 AC XY: 31792 AN XY: 130626

Gnomad AFR exome AF: 0.515

Gnomad AMR exome AF: 0.325

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.0284

Gnomad SAS exome AF: 0.141

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.265 AC: 386252 AN: 1456358 Hom.: 54971 Cov.: 40 AF XY: 0.261 AC XY: 188798 AN XY: 724230

Gnomad4 AFR exome AF: 0.522

Gnomad4 AMR exome AF: 0.323

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.0229

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.326 AC: 49391 AN: 151634 Hom.: 9387 Cov.: 31 AF XY: 0.315 AC XY: 23339 AN XY: 74062

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.331

Alfa AF: 0.261 Hom.: 2304

Bravo AF: 0.345

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4 Other:1

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided Benign:1 Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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	-0.90
CADD	Benign	5.1
DANN	Benign	0.76

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: rs1061505; hg19: chr11-613297;