chr1-159032432-A-G

Variant names:

• chr1-159032432-A-G
• rs861318
• NM_001376587.1:c.1162-92A>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.1162-92A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 750,968 control chromosomes in the GnomAD database, including 223,809 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 0.70 (40261 hom., cov: 31)
  • Exomes 𝑓: 0.78 (183548 hom.)
• Consequence: IFI16 NM_001376587.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.824 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI16	NM_001376587.1	MANE Select	c.1162-92A>G		intron	N/A	NP_001363516.1
	IFI16	NM_001364867.2		c.1162-92A>G		intron	N/A	NP_001351796.1
	IFI16	NM_001206567.2		c.994-92A>G		intron	N/A	NP_001193496.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI16	ENST00000295809.12	TSL:5 MANE Select	c.1162-92A>G		intron	N/A	ENSP00000295809.7
	IFI16	ENST00000368131.8	TSL:1	c.1162-92A>G		intron	N/A	ENSP00000357113.4
	IFI16	ENST00000368132.7	TSL:1	c.1162-92A>G		intron	N/A	ENSP00000357114.3

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106783 AN: 152028 Hom.: 40248 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.737

GnomAD4 exome AF: 0.778 AC: 465789 AN: 598822 Hom.: 183548 AF XY: 0.777 AC XY: 238122 AN XY: 306348

African (AFR) AF: 0.366 AC: 5492 AN: 15000

American (AMR) AF: 0.839 AC: 10450 AN: 12448

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 10614 AN: 13192

East Asian (EAS) AF: 0.686 AC: 19357 AN: 28212

South Asian (SAS) AF: 0.683 AC: 23643 AN: 34622

European-Finnish (FIN) AF: 0.839 AC: 32059 AN: 38218

Middle Eastern (MID) AF: 0.761 AC: 2807 AN: 3688

European-Non Finnish (NFE) AF: 0.800 AC: 338621 AN: 423436

Other (OTH) AF: 0.758 AC: 22746 AN: 30006

GnomAD4 genome AF: 0.702 AC: 106836 AN: 152146 Hom.: 40261 Cov.: 31 AF XY: 0.708 AC XY: 52679 AN XY: 74378

African (AFR) AF: 0.409 AC: 16965 AN: 41462

American (AMR) AF: 0.836 AC: 12791 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2787 AN: 3466

East Asian (EAS) AF: 0.640 AC: 3309 AN: 5172

South Asian (SAS) AF: 0.719 AC: 3475 AN: 4830

European-Finnish (FIN) AF: 0.861 AC: 9118 AN: 10594

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55805 AN: 68006

Other (OTH) AF: 0.740 AC: 1564 AN: 2114

Alfa AF: 0.772 Hom.: 128642

Bravo AF: 0.691

Asia WGS AF: 0.661 AC: 2298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.8
DANN	Benign	0.83
PhyloP100		-0.31
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: rs861318; hg19: chr1-159002222; COSMIC: COSV55535389; COSMIC: COSV55535389;