chr11-613297-T-G

Variant names:

• chr11-613297-T-G
• rs1061505
• NM_001572.5:c.1146A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001572.5(IRF7):​c.1146A>C​(p.Gly382Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,607,992 control chromosomes in the GnomAD database, including 64,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G382G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.33 (9387 hom., cov: 31)
  • Exomes 𝑓: 0.27 (54971 hom.)
• Consequence: IRF7 NM_001572.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: -1.78
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-613297-T-G is Benign according to our data. Variant chr11-613297-T-G is described in ClinVar as Benign. ClinVar VariationId is 1170387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.78 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF7	NM_001572.5	MANE Select	c.1146A>C	p.Gly382Gly	synonymous	Exon 9 of 11	NP_001563.2
	IRF7	NM_004031.4		c.1185A>C	p.Gly395Gly	synonymous	Exon 8 of 10	NP_004022.2	Q92985-4
	IRF7	NM_001440440.1		c.1182A>C	p.Gly394Gly	synonymous	Exon 8 of 10	NP_001427369.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF7	ENST00000525445.6	TSL:5 MANE Select	c.1146A>C	p.Gly382Gly	synonymous	Exon 9 of 11	ENSP00000434009.2	Q92985-1
	IRF7	ENST00000397566.5	TSL:1	c.1185A>C	p.Gly395Gly	synonymous	Exon 7 of 9	ENSP00000380697.1	Q92985-4
	IRF7	ENST00000397570.5	TSL:1	c.1098A>C	p.Gly366Gly	synonymous	Exon 6 of 8	ENSP00000380700.2	M9RSF4

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49340 AN: 151520 Hom.: 9371 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.333

GnomAD2 exomes AF: 0.252 AC: 60036 AN: 237930 AF XY: 0.243

Gnomad AFR exome AF: 0.515

Gnomad AMR exome AF: 0.325

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.0284

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.265 AC: 386252 AN: 1456358 Hom.: 54971 Cov.: 40 AF XY: 0.261 AC XY: 188798 AN XY: 724230

African (AFR) AF: 0.522 AC: 17425 AN: 33384

American (AMR) AF: 0.323 AC: 14217 AN: 44034

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 8684 AN: 25922

East Asian (EAS) AF: 0.0229 AC: 905 AN: 39536

South Asian (SAS) AF: 0.143 AC: 12276 AN: 85890

European-Finnish (FIN) AF: 0.198 AC: 10210 AN: 51604

Middle Eastern (MID) AF: 0.306 AC: 1753 AN: 5728

European-Non Finnish (NFE) AF: 0.274 AC: 304376 AN: 1110098

Other (OTH) AF: 0.273 AC: 16406 AN: 60162

GnomAD4 genome AF: 0.326 AC: 49391 AN: 151634 Hom.: 9387 Cov.: 31 AF XY: 0.315 AC XY: 23339 AN XY: 74062

African (AFR) AF: 0.519 AC: 21478 AN: 41394

American (AMR) AF: 0.307 AC: 4685 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1204 AN: 3464

East Asian (EAS) AF: 0.0255 AC: 130 AN: 5108

South Asian (SAS) AF: 0.128 AC: 612 AN: 4794

European-Finnish (FIN) AF: 0.186 AC: 1963 AN: 10532

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

European-Non Finnish (NFE) AF: 0.270 AC: 18334 AN: 67790

Other (OTH) AF: 0.331 AC: 696 AN: 2102

Alfa AF: 0.274 Hom.: 3812

Bravo AF: 0.345

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Immunodeficiency 39 (2)
-	-	1	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.76
PhyloP100		-1.8
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: rs1061505; hg19: chr11-613297; COSMIC: COSV108058876; COSMIC: COSV108058876;