11-615011-A-T

Variant names:

• chr11-615011-A-T
• rs12272434
• NM_001572.5:c.184-4T>A

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.184-4T>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 1,542,720 control chromosomes in the GnomAD database, including 61,954 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9266 hom., cov: 35)
  • Exomes 𝑓: 0.27 (52688 hom.)
• Consequence: IRF7 NM_001572.5 splice_region, intron
• Scores: Splicing: ADA: 0.00009671
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.444
• Publications: 17 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=-0.91).
• BP6: Variant 11-615011-A-T is Benign according to our data. Variant chr11-615011-A-T is described in ClinVar as [Benign]. Clinvar id is 1170391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF7	NM_001572.5	c.184-4T>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.184-4T>A		splice_region_variant, intron_variant	Intron 3 of 10	5	NM_001572.5	ENSP00000434009.2

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49144 AN: 151834 Hom.: 9250 Cov.: 35

Gnomad AFR AF: 0.515

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: 0.330

GnomAD2 exomes AF: 0.248 AC: 40610 AN: 163470 AF XY: 0.239

Gnomad AFR exome AF: 0.510

Gnomad AMR exome AF: 0.318

Gnomad ASJ exome AF: 0.339

Gnomad EAS exome AF: 0.0282

Gnomad FIN exome AF: 0.186

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.266 AC: 369688 AN: 1390768 Hom.: 52688 Cov.: 37 AF XY: 0.261 AC XY: 179109 AN XY: 685460

African (AFR) AF: 0.520 AC: 16740 AN: 32176

American (AMR) AF: 0.316 AC: 12276 AN: 38832

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 7684 AN: 22914

East Asian (EAS) AF: 0.0224 AC: 860 AN: 38312

South Asian (SAS) AF: 0.145 AC: 11246 AN: 77376

European-Finnish (FIN) AF: 0.199 AC: 7349 AN: 36850

Middle Eastern (MID) AF: 0.306 AC: 1703 AN: 5566

European-Non Finnish (NFE) AF: 0.274 AC: 296115 AN: 1081060

Other (OTH) AF: 0.272 AC: 15715 AN: 57682

GnomAD4 genome AF: 0.324 AC: 49196 AN: 151952 Hom.: 9266 Cov.: 35 AF XY: 0.313 AC XY: 23261 AN XY: 74314

African (AFR) AF: 0.515 AC: 21312 AN: 41380

American (AMR) AF: 0.306 AC: 4672 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1200 AN: 3466

East Asian (EAS) AF: 0.0259 AC: 134 AN: 5176

South Asian (SAS) AF: 0.129 AC: 625 AN: 4832

European-Finnish (FIN) AF: 0.185 AC: 1961 AN: 10612

Middle Eastern (MID) AF: 0.341 AC: 99 AN: 290

European-Non Finnish (NFE) AF: 0.270 AC: 18311 AN: 67900

Other (OTH) AF: 0.329 AC: 695 AN: 2114

Alfa AF: 0.203 Hom.: 641

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 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

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	-0.91
CADD	Benign	2.4
DANN	Benign	0.92
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000097
dbscSNV1_RF	Benign	0.028
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

Other links and lift over

dbSNP: rs12272434; hg19: chr11-615011;