rs12290989

Variant names:

• chr11-615010-G-T
• rs12290989
• NM_001572.5:c.184-3C>A

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.184-3C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,542,680 control chromosomes in the GnomAD database, including 62,014 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9295 hom., cov: 35)
  • Exomes 𝑓: 0.27 (52719 hom.)
• Consequence: IRF7 NM_001572.5 splice_region, intron
• Scores: Splicing: ADA: 0.2375
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.66

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=-0.79).
• BP6: Variant 11-615010-G-T is Benign according to our data. Variant chr11-615010-G-T is described in ClinVar as [Benign]. Clinvar id is 1170390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF7	NM_001572.5	c.184-3C>A		splice_region_variant, intron_variant	Intron 3 of 10	ENST00000525445.6	NP_001563.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF7	ENST00000525445.6	c.184-3C>A		splice_region_variant, intron_variant	Intron 3 of 10	5	NM_001572.5	ENSP00000434009.2

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49210 AN: 151888 Hom.: 9279 Cov.: 35

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.0258

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.333

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.331

GnomAD3 exomes AF: 0.250 AC: 40766 AN: 163132 Hom.: 6038 AF XY: 0.241 AC XY: 21576 AN XY: 89642

Gnomad AFR exome AF: 0.513

Gnomad AMR exome AF: 0.319

Gnomad ASJ exome AF: 0.338

Gnomad EAS exome AF: 0.0283

Gnomad SAS exome AF: 0.140

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.256

GnomAD4 exome AF: 0.266 AC: 369805 AN: 1390674 Hom.: 52719 Cov.: 37 AF XY: 0.261 AC XY: 179184 AN XY: 685366

Gnomad4 AFR exome AF: 0.522

Gnomad4 AMR exome AF: 0.316

Gnomad4 ASJ exome AF: 0.336

Gnomad4 EAS exome AF: 0.0224

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.324 AC: 49262 AN: 152006 Hom.: 9295 Cov.: 35 AF XY: 0.313 AC XY: 23292 AN XY: 74338

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.0258

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.330

Alfa AF: 0.301 Hom.: 1409

Bravo AF: 0.345

Asia WGS AF: 0.127 AC: 440 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency 39 Benign:2

Jul 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 07, 2020

GeneDx

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	18
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.24
dbscSNV1_RF	Benign	0.39
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: -26
DS_AL_spliceai		0.25		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12290989; hg19: chr11-615010;