NM_001572.5:c.860G>C

Variant names:

• chr11-613583-C-G
• rs763456786
• NM_001572.5:c.860G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001572.5(IRF7):​c.860G>C​(p.Gly287Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000474 in 1,562,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G287R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: IRF7 NM_001572.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0730
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0662542).

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.860G>C	p.Gly287Ala	missense	Exon 9 of 11	NP_001563.2
	IRF7	NM_004031.4		c.899G>C	p.Gly300Ala	missense	Exon 8 of 10	NP_004022.2	Q92985-4
	IRF7	NM_001440440.1		c.896G>C	p.Gly299Ala	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.860G>C	p.Gly287Ala	missense	Exon 9 of 11	ENSP00000434009.2	Q92985-1
	IRF7	ENST00000397566.5	TSL:1	c.899G>C	p.Gly300Ala	missense	Exon 7 of 9	ENSP00000380697.1	Q92985-4
	IRF7	ENST00000397570.5	TSL:1	c.812G>C	p.Gly271Ala	missense	Exon 6 of 8	ENSP00000380700.2	M9RSF4

Frequencies

GnomAD3 genomes AF: 0.0000265 AC: 4 AN: 150704 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000591

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000517 AC: 10 AN: 193418 AF XY: 0.0000378

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000103

Gnomad OTH exome AF: 0.000215

GnomAD4 exome AF: 0.0000496 AC: 70 AN: 1412120 Hom.: 0 Cov.: 37 AF XY: 0.0000386 AC XY: 27 AN XY: 699228

African (AFR) AF: 0.00 AC: 0 AN: 31972

American (AMR) AF: 0.00 AC: 0 AN: 36706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22786

East Asian (EAS) AF: 0.00 AC: 0 AN: 38908

South Asian (SAS) AF: 0.00 AC: 0 AN: 78224

European-Finnish (FIN) AF: 0.0000202 AC: 1 AN: 49612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5130

European-Non Finnish (NFE) AF: 0.0000624 AC: 68 AN: 1090542

Other (OTH) AF: 0.0000172 AC: 1 AN: 58240

GnomAD4 genome AF: 0.0000265 AC: 4 AN: 150704 Hom.: 0 Cov.: 30 AF XY: 0.0000136 AC XY: 1 AN XY: 73508

African (AFR) AF: 0.00 AC: 0 AN: 41118

American (AMR) AF: 0.00 AC: 0 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 4994

South Asian (SAS) AF: 0.00 AC: 0 AN: 4708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000591 AC: 4 AN: 67662

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.000144 Hom.: 1

ExAC AF: 0.0000670 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Immunodeficiency 39 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.8
DANN	Benign	0.81
DEOGEN2	Benign	0.075	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.073
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.025
Sift	Benign	0.37	T
Sift4G	Benign	0.70	T
Polyphen		0.26	B
Vest4		0.15
MVP		0.45
MPC		0.13
ClinPred		0.065	T
GERP RS		2.1
Varity_R		0.057
gMVP		0.39
Mutation Taster		=88/12	polymorphism

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: rs763456786; hg19: chr11-613583;