1-159018529-C-T

Variant names:

• chr1-159018529-C-T
• rs149606671
• NM_001376587.1:c.850C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001376587.1(IFI16):​c.850C>T​(p.Pro284Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00825 in 1,613,796 control chromosomes in the GnomAD database, including 61 homozygotes. 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P284T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0057 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (60 hom.)
• Consequence: IFI16 NM_001376587.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.79
• Publications: 12 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004410118).
• BP6: Variant 1-159018529-C-T is Benign according to our data. Variant chr1-159018529-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2639482.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 60 AR gene

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.850C>T	p.Pro284Ser	missense	Exon 5 of 12	NP_001363516.1	Q16666-1
	IFI16	NM_001364867.2		c.850C>T	p.Pro284Ser	missense	Exon 6 of 13	NP_001351796.1	Q16666-1
	IFI16	NM_001206567.2		c.682C>T	p.Pro228Ser	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.850C>T	p.Pro284Ser	missense	Exon 5 of 12	ENSP00000295809.7	Q16666-1
	IFI16	ENST00000368131.8	TSL:1	c.850C>T	p.Pro284Ser	missense	Exon 5 of 11	ENSP00000357113.4	Q16666-2
	IFI16	ENST00000368132.7	TSL:1	c.850C>T	p.Pro284Ser	missense	Exon 5 of 11	ENSP00000357114.3	Q16666-2

Frequencies

GnomAD3 genomes AF: 0.00571 AC: 869 AN: 152138 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00915

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00586 AC: 1474 AN: 251336 AF XY: 0.00595

Gnomad AFR exome AF: 0.00160

Gnomad AMR exome AF: 0.00428

Gnomad ASJ exome AF: 0.0194

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00189

Gnomad NFE exome AF: 0.00851

Gnomad OTH exome AF: 0.00751

GnomAD4 exome AF: 0.00851 AC: 12439 AN: 1461540 Hom.: 60 Cov.: 31 AF XY: 0.00842 AC XY: 6122 AN XY: 727100

African (AFR) AF: 0.00119 AC: 40 AN: 33474

American (AMR) AF: 0.00449 AC: 201 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0201 AC: 524 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.00155 AC: 134 AN: 86246

European-Finnish (FIN) AF: 0.00206 AC: 110 AN: 53418

Middle Eastern (MID) AF: 0.00693 AC: 40 AN: 5768

European-Non Finnish (NFE) AF: 0.00976 AC: 10852 AN: 1111716

Other (OTH) AF: 0.00889 AC: 537 AN: 60380

GnomAD4 genome AF: 0.00570 AC: 868 AN: 152256 Hom.: 1 Cov.: 32 AF XY: 0.00516 AC XY: 384 AN XY: 74460

African (AFR) AF: 0.00169 AC: 70 AN: 41536

American (AMR) AF: 0.00490 AC: 75 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00915 AC: 622 AN: 68006

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00818 Hom.: 15

Bravo AF: 0.00603

TwinsUK AF: 0.0111 AC: 41

ALSPAC AF: 0.0145 AC: 56

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.00988 AC: 85

ExAC AF: 0.00539 AC: 655

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00911

EpiControl AF: 0.0104

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.1
DANN	Benign	0.95
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PhyloP100		-1.8
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.028
Sift	Uncertain	0.023	D
Sift4G	Benign	0.33	T
Polyphen		0.091	B
Vest4		0.20
MVP		0.23
MPC		0.26
ClinPred		0.023	T
GERP RS		-2.6
Varity_R		0.11
gMVP		0.022
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

dbSNP: rs149606671; hg19: chr1-158988319; COSMIC: COSV99856939; COSMIC: COSV99856939;