rs376350717

Positions:

• chr11-614874-A-G
• chr11-614874-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001572.5(IRF7):​c.317T>C​(p.Val106Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: IRF7 NM_001572.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21025124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF7	NM_001572.5	c.317T>C	p.Val106Ala	missense_variant	4/11	ENST00000525445.6	NP_001563.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF7	ENST00000525445.6	c.317T>C	p.Val106Ala	missense_variant	4/11	5	NM_001572.5	ENSP00000434009	P2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426270 Hom.: 0 Cov.: 37 AF XY: 0.00000141 AC XY: 1 AN XY: 706910

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.12e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	16
DANN	Benign	0.68
DEOGEN2	Uncertain	0.59	D;.;.;D;T;.;.;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.65	.;T;T;T;T;.;T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.33	D
MutationAssessor	Uncertain	2.2	M;.;M;M;.;.;.;.
MutationTaster	Benign	1.0	D;D;N;N;N;N;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.7	N;N;N;.;.;N;.;.
REVEL	Uncertain	0.39
Sift	Benign	0.34	T;T;T;.;.;T;.;.
Sift4G	Benign	0.86	T;T;T;.;T;T;.;.
Polyphen		0.84	P;P;P;P;.;P;.;.
Vest4		0.22
MutPred		0.35		Gain of disorder (P = 0.033);.;Gain of disorder (P = 0.033);Gain of disorder (P = 0.033);.;.;Gain of disorder (P = 0.033);.;
MVP		0.85
MPC		0.32
ClinPred		0.14	T
GERP RS		0.45
Varity_R		0.078
gMVP		0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs376350717; hg19: chr11-614874;