chr1-159035859-A-G

Position:

• chr1-159035859-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001376587.1(IFI16):​c.1329+3168A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 151,902 control chromosomes in the GnomAD database, including 41,187 homozygotes. 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: 𝑓 0.72 (41187 hom., cov: 30)
• Consequence: IFI16 NM_001376587.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFI16	NM_001376587.1	c.1329+3168A>G		intron_variant		ENST00000295809.12	NP_001363516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFI16	ENST00000295809.12	c.1329+3168A>G		intron_variant		5	NM_001376587.1	ENSP00000295809	A2

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109552 AN: 151784 Hom.: 41184 Cov.: 30

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.740

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.721 AC: 109587 AN: 151902 Hom.: 41187 Cov.: 30 AF XY: 0.726 AC XY: 53921 AN XY: 74250

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.707

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.743

Alfa AF: 0.793 Hom.: 45345

Bravo AF: 0.713

Asia WGS AF: 0.637 AC: 2214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.46

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: rs1772408; hg19: chr1-159005649;