11-612967-A-G

Variant names:

• chr11-612967-A-G
• rs11246213
• NM_001572.5:c.1356+32T>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.1356+32T>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 1,605,328 control chromosomes in the GnomAD database, including 64,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9395 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54811 hom.)
• Consequence: IRF7 NM_001572.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.64
• Publications: 24 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=-0.97).
• BP6: Variant 11-612967-A-G is Benign according to our data. Variant chr11-612967-A-G is described in ClinVar as Benign. ClinVar VariationId is 1185463.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.1356+32T>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.1356+32T>C		intron_variant	Intron 10 of 10	5	NM_001572.5	ENSP00000434009.2

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49370 AN: 151908 Hom.: 9379 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.0255

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: 0.254 AC: 63399 AN: 249288 AF XY: 0.244

Gnomad AFR exome AF: 0.523

Gnomad AMR exome AF: 0.324

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.0283

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.268

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.265 AC: 385219 AN: 1453304 Hom.: 54811 Cov.: 31 AF XY: 0.260 AC XY: 188365 AN XY: 723276

African (AFR) AF: 0.522 AC: 17389 AN: 33298

American (AMR) AF: 0.321 AC: 14309 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 8697 AN: 25962

East Asian (EAS) AF: 0.0228 AC: 906 AN: 39652

South Asian (SAS) AF: 0.143 AC: 12287 AN: 86048

European-Finnish (FIN) AF: 0.199 AC: 10395 AN: 52308

Middle Eastern (MID) AF: 0.305 AC: 1748 AN: 5740

European-Non Finnish (NFE) AF: 0.274 AC: 303113 AN: 1105644

Other (OTH) AF: 0.273 AC: 16375 AN: 60078

GnomAD4 genome AF: 0.325 AC: 49421 AN: 152024 Hom.: 9395 Cov.: 32 AF XY: 0.314 AC XY: 23357 AN XY: 74326

African (AFR) AF: 0.519 AC: 21490 AN: 41444

American (AMR) AF: 0.307 AC: 4697 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3470

East Asian (EAS) AF: 0.0255 AC: 132 AN: 5170

South Asian (SAS) AF: 0.128 AC: 614 AN: 4814

European-Finnish (FIN) AF: 0.185 AC: 1958 AN: 10594

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

European-Non Finnish (NFE) AF: 0.270 AC: 18342 AN: 67926

Other (OTH) AF: 0.330 AC: 695 AN: 2106

Alfa AF: 0.297 Hom.: 9298

Bravo AF: 0.345

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	-0.97
CADD	Benign	0.43
DANN	Benign	0.43
PhyloP100		-1.6
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

Other links and lift over

dbSNP: rs11246213; hg19: chr11-612967; COSMIC: COSV52762490; COSMIC: COSV52762490;