chr1-159018233-C-T

Variant names:

• chr1-159018233-C-T
• rs751208160
• NM_001376587.1:c.554C>T

Variant summary

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

The NM_001376587.1(IFI16):​c.554C>T​(p.Pro185Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,460,690 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: IFI16 NM_001376587.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.20
• Publications: 1 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: 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=0.02868998).

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.554C>T	p.Pro185Leu	missense	Exon 5 of 12	NP_001363516.1	Q16666-1
	IFI16	NM_001364867.2		c.554C>T	p.Pro185Leu	missense	Exon 6 of 13	NP_001351796.1	Q16666-1
	IFI16	NM_001206567.2		c.386C>T	p.Pro129Leu	missense	Exon 4 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.554C>T	p.Pro185Leu	missense	Exon 5 of 12	ENSP00000295809.7	Q16666-1
	IFI16	ENST00000368131.8	TSL:1	c.554C>T	p.Pro185Leu	missense	Exon 5 of 11	ENSP00000357113.4	Q16666-2
	IFI16	ENST00000368132.7	TSL:1	c.554C>T	p.Pro185Leu	missense	Exon 5 of 11	ENSP00000357114.3	Q16666-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000479 AC: 12 AN: 250710 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000490

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000240 AC: 35 AN: 1460690 Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17 AN XY: 726650

African (AFR) AF: 0.0000300 AC: 1 AN: 33324

American (AMR) AF: 0.0000225 AC: 1 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39686

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111406

Other (OTH) AF: 0.000166 AC: 10 AN: 60320

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000824 AC: 10

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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	0.093
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.85
DANN	Benign	0.57
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.11	N
PhyloP100		-1.2
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Benign	0.55	T
Sift4G	Benign	0.36	T
Polyphen		0.99	D
Vest4		0.17
MutPred		0.22		Loss of catalytic residue at P185 (P = 0.0172)
MVP		0.32
MPC		0.32
ClinPred		0.12	T
GERP RS		-5.6
Varity_R		0.019
gMVP		0.036
Mutation Taster		=85/15	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: rs751208160; hg19: chr1-158988023;