11-614193-C-T

Variant names:

• chr11-614193-C-T
• rs76107421
• NM_001572.5:c.660G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001572.5(IRF7):​c.660G>A​(p.Leu220Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000713 in 1,612,802 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L220L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (3 hom.)
• Consequence: IRF7 NM_001572.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.78
• Publications: 0 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-614193-C-T is Benign according to our data. Variant chr11-614193-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 476073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.78 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.660G>A	p.Leu220Leu	synonymous	Exon 6 of 11	NP_001563.2
	IRF7	NM_004031.4		c.699G>A	p.Leu233Leu	synonymous	Exon 5 of 10	NP_004022.2
	IRF7	NM_001440440.1		c.696G>A	p.Leu232Leu	synonymous	Exon 5 of 10	NP_001427369.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF7	ENST00000525445.6	TSL:5 MANE Select	c.660G>A	p.Leu220Leu	synonymous	Exon 6 of 11	ENSP00000434009.2
	IRF7	ENST00000397566.5	TSL:1	c.699G>A	p.Leu233Leu	synonymous	Exon 4 of 9	ENSP00000380697.1
	IRF7	ENST00000397570.5	TSL:1	c.699G>A	p.Leu233Leu	synonymous	Exon 4 of 8	ENSP00000380700.2

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 573 AN: 152196 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.000866 AC: 215 AN: 248158 AF XY: 0.000601

Gnomad AFR exome AF: 0.0123

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000539

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000394 AC: 575 AN: 1460488 Hom.: 3 Cov.: 35 AF XY: 0.000344 AC XY: 250 AN XY: 726496

African (AFR) AF: 0.0141 AC: 473 AN: 33474

American (AMR) AF: 0.000515 AC: 23 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1111846

Other (OTH) AF: 0.000679 AC: 41 AN: 60358

GnomAD4 genome AF: 0.00378 AC: 575 AN: 152314 Hom.: 3 Cov.: 32 AF XY: 0.00372 AC XY: 277 AN XY: 74478

African (AFR) AF: 0.0133 AC: 553 AN: 41566

American (AMR) AF: 0.000784 AC: 12 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.00196 Hom.: 1

Bravo AF: 0.00437

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Immunodeficiency 39 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.57
DANN	Benign	0.77
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs76107421; hg19: chr11-614193;