Variant 11-615011-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Variant links:

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 links:

IRF7 (HGNC:):

IRF7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IRF7	NM_001572.5 linkuse as main transcript	c.184-4T>A		splice_region_variant, intron_variant		ENST00000525445.6	NP_001563.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF7	ENST00000525445.6 linkuse as main transcript	c.184-4T>A		splice_region_variant, intron_variant		5	NM_001572.5	ENSP00000434009.2		Q92985-1

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

49144

AN:

151834

Hom.:

9250

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.248

AC:

40610

AN:

163470

Hom.:

5995

AF XY:

0.239

AC XY:

21478

AN XY:

89888

show subpopulations

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 SAS exome

AF:

0.139

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.:

AF XY:

0.261

AC XY:

179109

AN XY:

685460

show subpopulations

Gnomad4 AFR exome

AF:

0.520

Gnomad4 AMR exome

AF:

0.316

Gnomad4 ASJ exome

AF:

0.335

Gnomad4 EAS exome

AF:

0.0224

Gnomad4 SAS exome

AF:

0.145

Gnomad4 FIN exome

AF:

0.199

Gnomad4 NFE exome

AF:

0.274

Gnomad4 OTH exome

AF:

0.272

GnomAD4 genome

AF:

0.324

AC:

49196

AN:

151952

Hom.:

9266

Cov.:

AF XY:

0.313

AC XY:

23261

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.515

Gnomad4 AMR

AF:

0.306

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.0259

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.185

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.329

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

LINK: link

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	Aug 11, 2023	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 07, 2020	- -

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

-0.91

CADD

Benign

2.4

DANN

Benign

0.92

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over