1-159035859-A-G

Variant names:

• chr1-159035859-A-G
• rs1772408
• NM_001376587.1:c.1329+3168A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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: Benign. The variant received -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.

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.1329+3168A>G		intron	N/A	NP_001363516.1	Q16666-1
	IFI16	NM_001364867.2		c.1329+3168A>G		intron	N/A	NP_001351796.1	Q16666-1
	IFI16	NM_001206567.2		c.1161+3168A>G		intron	N/A	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.1329+3168A>G		intron	N/A	ENSP00000295809.7	Q16666-1
	IFI16	ENST00000368131.8	TSL:1	c.1329+3168A>G		intron	N/A	ENSP00000357113.4	Q16666-2
	IFI16	ENST00000368132.7	TSL:1	c.1329+3168A>G		intron	N/A	ENSP00000357114.3	Q16666-2

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

African (AFR) AF: 0.496 AC: 20523 AN: 41358

American (AMR) AF: 0.828 AC: 12643 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2781 AN: 3470

East Asian (EAS) AF: 0.627 AC: 3234 AN: 5160

South Asian (SAS) AF: 0.707 AC: 3402 AN: 4814

European-Finnish (FIN) AF: 0.853 AC: 8993 AN: 10546

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55431 AN: 67972

Other (OTH) AF: 0.743 AC: 1567 AN: 2110

Alfa AF: 0.767 Hom.: 82331

Bravo AF: 0.713

Asia WGS AF: 0.637 AC: 2214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.46
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs1772408; hg19: chr1-159005649;