IRF7 p.Ser333Arg

Variant names:

• chr11-613446-T-G
• NM_001572.5:c.997A>C
• IRF7 p.Ser333Arg

Your query was ambiguous. Multiple possible variants found:

• chr11-613446-T-G
• chr11-613444-G-T
• chr11-613444-G-C
• chr11-613444-GCT-ACG
• chr11-613444-GCT-TCG
• chr11-613444-GCT-CCG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001572.5(IRF7):​c.997A>C​(p.Ser333Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S333N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: IRF7 NM_001572.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.997A>C	p.Ser333Arg	missense	Exon 9 of 11	NP_001563.2
	IRF7	NM_004031.4		c.1036A>C	p.Ser346Arg	missense	Exon 8 of 10	NP_004022.2	Q92985-4
	IRF7	NM_001440440.1		c.1033A>C	p.Ser345Arg	missense	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.997A>C	p.Ser333Arg	missense	Exon 9 of 11	ENSP00000434009.2	Q92985-1
	IRF7	ENST00000397566.5	TSL:1	c.1036A>C	p.Ser346Arg	missense	Exon 7 of 9	ENSP00000380697.1	Q92985-4
	IRF7	ENST00000397570.5	TSL:1	c.949A>C	p.Ser317Arg	missense	Exon 6 of 8	ENSP00000380700.2	M9RSF4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		2.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Varity_R		0.79
gMVP		0.68
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-613446;