11-612843-T-G

Variant names:

• chr11-612843-T-G
• rs10902178
• NM_001572.5:c.1357-43A>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.1357-43A>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 1,597,786 control chromosomes in the GnomAD database, including 64,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9371 hom., cov: 31)
  • Exomes 𝑓: 0.27 (54730 hom.)
• Consequence: IRF7 NM_001572.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.218

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 11-612843-T-G is Benign according to our data. Variant chr11-612843-T-G is described in ClinVar as [Benign]. Clinvar id is 1185462.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.1357-43A>C		intron_variant	Intron 10 of 10	ENST00000525445.6	NP_001563.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF7	ENST00000525445.6	c.1357-43A>C		intron_variant	Intron 10 of 10	5	NM_001572.5	ENSP00000434009.2

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49287 AN: 151568 Hom.: 9355 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.0258

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.333

GnomAD2 exomes AF: 0.255 AC: 61646 AN: 241498 AF XY: 0.244

Gnomad AFR exome AF: 0.522

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.336

Gnomad EAS exome AF: 0.0281

Gnomad FIN exome AF: 0.190

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.266 AC: 384082 AN: 1446098 Hom.: 54730 Cov.: 37 AF XY: 0.261 AC XY: 187489 AN XY: 718334

Gnomad4 AFR exome AF: 0.523 AC: 17413 AN: 33324

Gnomad4 AMR exome AF: 0.321 AC: 14306 AN: 44510

Gnomad4 ASJ exome AF: 0.335 AC: 8717 AN: 26004

Gnomad4 EAS exome AF: 0.0228 AC: 901 AN: 39478

Gnomad4 SAS exome AF: 0.143 AC: 12309 AN: 86016

Gnomad4 FIN exome AF: 0.198 AC: 9090 AN: 45828

Gnomad4 NFE exome AF: 0.274 AC: 303495 AN: 1106004

Gnomad4 Remaining exome AF: 0.273 AC: 16348 AN: 59888

GnomAD4 genome AF: 0.325 AC: 49338 AN: 151688 Hom.: 9371 Cov.: 31 AF XY: 0.314 AC XY: 23300 AN XY: 74116

Gnomad4 AFR AF: 0.519 AC: 0.51914 AN: 0.51914

Gnomad4 AMR AF: 0.307 AC: 0.306915 AN: 0.306915

Gnomad4 ASJ AF: 0.347 AC: 0.346774 AN: 0.346774

Gnomad4 EAS AF: 0.0258 AC: 0.0258453 AN: 0.0258453

Gnomad4 SAS AF: 0.128 AC: 0.128339 AN: 0.128339

Gnomad4 FIN AF: 0.185 AC: 0.18482 AN: 0.18482

Gnomad4 NFE AF: 0.270 AC: 0.269966 AN: 0.269966

Gnomad4 OTH AF: 0.331 AC: 0.330959 AN: 0.330959

Alfa AF: 0.294 Hom.: 7967

Bravo AF: 0.346

Asia WGS AF: 0.125 AC: 437 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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. -

Immunodeficiency 39 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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	-0.95
CADD	Benign	2.5
DANN	Benign	0.65
Mutation Taster		=100/0	polymorphism (auto)

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: rs10902178; hg19: chr11-612843; COSMIC: COSV52764777; COSMIC: COSV52764777;