NM_001376587.1:c.232C>G

Variant names:

• chr1-159014912-C-G
• NM_001376587.1:c.232C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001376587.1(IFI16):​c.232C>G​(p.Leu78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFI16 NM_001376587.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.63
• Publications: 0 publications found

Genes affected

IFI16 (HGNC:5395): (interferon gamma inducible protein 16) This gene encodes a member of the HIN-200 (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats) family of cytokines. The encoded protein contains domains involved in DNA binding, transcriptional regulation, and protein-protein interactions. The protein localizes to the nucleoplasm and nucleoli, and interacts with p53 and retinoblastoma-1. It modulates p53 function, and inhibits cell growth in the Ras/Raf signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16208991).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376587.1. 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
	IFI16	NM_001376587.1	MANE Select	c.232C>G	p.Leu78Val	missense	Exon 2 of 12	NP_001363516.1	Q16666-1
	IFI16	NM_001364867.2		c.232C>G	p.Leu78Val	missense	Exon 3 of 13	NP_001351796.1	Q16666-1
	IFI16	NM_001206567.2		c.232C>G	p.Leu78Val	missense	Exon 2 of 11	NP_001193496.1	Q16666-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI16	ENST00000295809.12	TSL:5 MANE Select	c.232C>G	p.Leu78Val	missense	Exon 2 of 12	ENSP00000295809.7	Q16666-1
	IFI16	ENST00000368131.8	TSL:1	c.232C>G	p.Leu78Val	missense	Exon 2 of 11	ENSP00000357113.4	Q16666-2
	IFI16	ENST00000368132.7	TSL:1	c.232C>G	p.Leu78Val	missense	Exon 2 of 11	ENSP00000357114.3	Q16666-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.23
DANN	Benign	0.97
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		-2.6
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.079
Sift	Benign	0.11	T
Sift4G	Benign	0.12	T
Polyphen		0.22	B
Vest4		0.18
MutPred		0.53		Gain of phosphorylation at T81 (P = 0.1193)
MVP		0.41
MPC		0.35
ClinPred		0.15	T
GERP RS		-1.3
PromoterAI		0.00030	Neutral
Varity_R		0.10
gMVP		0.14
Mutation Taster		=98/2	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

hg19: chr1-158984702;