rs6940

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001376587.1(IFI16):c.2335A>T(p.Thr779Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,591,424 control chromosomes in the GnomAD database, including 18,168 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2454 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15714 hom. )

Consequence

IFI16
NM_001376587.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.07

Publications

44 publications found

Variant links:

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]

IFI16 links:

AIM2 (HGNC:357): (absent in melanoma 2) AIM2 is a member of the IFI20X /IFI16 family. It plays a putative role in tumorigenic reversion and may control cell proliferation. Interferon-gamma induces expression of AIM2. [provided by RefSeq, Jul 2008]

AIM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050237477).

BP6

Variant 1-159054878-A-T is Benign according to our data. Variant chr1-159054878-A-T is described in ClinVar as Benign. ClinVar VariationId is 1230050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFI16	NM_001376587.1	MANE Select	c.2335A>T	p.Thr779Ser	missense	Exon 12 of 12	NP_001363516.1	Q16666-1
IFI16	NM_001364867.2		c.2335A>T	p.Thr779Ser	missense	Exon 13 of 13	NP_001351796.1	Q16666-1
IFI16	NM_001206567.2		c.2167A>T	p.Thr723Ser	missense	Exon 11 of 11	NP_001193496.1	Q16666-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFI16	ENST00000295809.12	TSL:5 MANE Select	c.2335A>T	p.Thr779Ser	missense	Exon 12 of 12	ENSP00000295809.7	Q16666-1
IFI16	ENST00000368131.8	TSL:1	c.2167A>T	p.Thr723Ser	missense	Exon 11 of 11	ENSP00000357113.4	Q16666-2
IFI16	ENST00000368132.7	TSL:1	c.2167A>T	p.Thr723Ser	missense	Exon 11 of 11	ENSP00000357114.3	Q16666-2

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25310

AN:

151990

Hom.:

2453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.0879

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.266

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.105

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.150

GnomAD2 exomes

AF:

0.153

AC:

37287

AN:

243370

AF XY:

0.157

show subpopulations

Gnomad AFR exome

AF:

0.237

Gnomad AMR exome

AF:

0.0681

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.309

Gnomad FIN exome

AF:

0.109

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.139

AC:

200378

AN:

1439316

Hom.:

15714

Cov.:

AF XY:

0.142

AC XY:

101841

AN XY:

716578

show subpopulations

African (AFR)

AF:

0.247

AC:

8125

AN:

32940

American (AMR)

AF:

0.0720

AC:

3179

AN:

44166

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

3106

AN:

25670

East Asian (EAS)

AF:

0.244

AC:

9632

AN:

39480

South Asian (SAS)

AF:

0.246

AC:

20831

AN:

84830

European-Finnish (FIN)

AF:

0.112

AC:

5920

AN:

53088

Middle Eastern (MID)

AF:

0.139

AC:

773

AN:

5568

European-Non Finnish (NFE)

AF:

0.128

AC:

139767

AN:

1093988

Other (OTH)

AF:

0.152

AC:

9045

AN:

59586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

6941

13882

20822

27763

34704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5196

10392

15588

20784

25980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.167

AC:

25327

AN:

152108

Hom.:

2454

Cov.:

AF XY:

0.164

AC XY:

12226

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.244

AC:

10123

AN:

41454

American (AMR)

AF:

0.0878

AC:

1343

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

437

AN:

3472

East Asian (EAS)

AF:

0.303

AC:

1567

AN:

5164

South Asian (SAS)

AF:

0.265

AC:

1281

AN:

4828

European-Finnish (FIN)

AF:

0.104

AC:

1104

AN:

10592

Middle Eastern (MID)

AF:

0.116

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.133

AC:

9011

AN:

68000

Other (OTH)

AF:

0.147

AC:

310

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1035

2070

3106

4141

5176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.140

Hom.:

1253

Bravo

AF:

0.165

TwinsUK

AF:

0.133

AC:

494

ALSPAC

AF:

0.127

AC:

490

ESP6500AA

AF:

0.231

AC:

1018

ESP6500EA

AF:

0.132

AC:

1136

ExAC

AF:

0.158

AC:

19172

Asia WGS

AF:

0.282

AC:

978

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.020

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0050

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.7

PhyloP100

1.1

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.84

REVEL

Benign

0.060

Sift

Benign

0.51

Sift4G

Benign

0.26

Polyphen

1.0

Vest4

0.26

MPC

0.034

ClinPred

0.020

GERP RS

3.5

Varity_R

0.20

gMVP

0.015

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over