11-613165-G-C

Variant names:

• chr11-613165-G-C
• rs1051390
• NM_001572.5:c.1237+41C>G

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+41C>G 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 1,601,674 control chromosomes in the GnomAD database, including 63,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9384 hom., cov: 32)
  • Exomes 𝑓: 0.26 (54300 hom.)
• Consequence: IRF7 NM_001572.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.299
• Publications: 13 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=-0.86).
• BP6: Variant 11-613165-G-C is Benign according to our data. Variant chr11-613165-G-C is described in ClinVar as Benign. ClinVar VariationId is 1185464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001572.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF7	NM_001572.5	MANE Select	c.1237+41C>G		intron	N/A	NP_001563.2
	IRF7	NM_004031.4		c.1276+41C>G		intron	N/A	NP_004022.2
	IRF7	NM_001440440.1		c.1273+41C>G		intron	N/A	NP_001427369.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF7	ENST00000525445.6	TSL:5 MANE Select	c.1237+41C>G		intron	N/A	ENSP00000434009.2
	IRF7	ENST00000397566.5	TSL:1	c.1276+41C>G		intron	N/A	ENSP00000380697.1
	IRF7	ENST00000397570.5	TSL:1	c.1189+41C>G		intron	N/A	ENSP00000380700.2

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49363 AN: 152050 Hom.: 9368 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.0251

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: 0.250 AC: 60151 AN: 240300 AF XY: 0.240

Gnomad AFR exome AF: 0.519

Gnomad AMR exome AF: 0.319

Gnomad ASJ exome AF: 0.336

Gnomad EAS exome AF: 0.0280

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.264 AC: 383172 AN: 1449506 Hom.: 54300 Cov.: 36 AF XY: 0.260 AC XY: 186952 AN XY: 719916

African (AFR) AF: 0.522 AC: 17250 AN: 33066

American (AMR) AF: 0.319 AC: 13847 AN: 43426

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 8576 AN: 25618

East Asian (EAS) AF: 0.0228 AC: 902 AN: 39518

South Asian (SAS) AF: 0.142 AC: 12201 AN: 85664

European-Finnish (FIN) AF: 0.198 AC: 10281 AN: 51846

Middle Eastern (MID) AF: 0.304 AC: 1739 AN: 5714

European-Non Finnish (NFE) AF: 0.273 AC: 302163 AN: 1104918

Other (OTH) AF: 0.271 AC: 16213 AN: 59736

GnomAD4 genome AF: 0.325 AC: 49414 AN: 152168 Hom.: 9384 Cov.: 32 AF XY: 0.314 AC XY: 23352 AN XY: 74402

African (AFR) AF: 0.518 AC: 21504 AN: 41510

American (AMR) AF: 0.307 AC: 4690 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1203 AN: 3472

East Asian (EAS) AF: 0.0251 AC: 130 AN: 5174

South Asian (SAS) AF: 0.128 AC: 616 AN: 4830

European-Finnish (FIN) AF: 0.185 AC: 1966 AN: 10612

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

European-Non Finnish (NFE) AF: 0.270 AC: 18318 AN: 67960

Other (OTH) AF: 0.330 AC: 697 AN: 2112

Alfa AF: 0.308 Hom.: 1416

Bravo AF: 0.345

Asia WGS AF: 0.126 AC: 439 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1051390; hg19: chr11-613165;