chr16-3656696-G-A

Position:

chr16-3656696-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005223.4(DNASE1):c.379G>A(p.Gly127Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00529 in 1,613,252 control chromosomes in the GnomAD database, including 168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 72 hom., cov: 31)

Exomes 𝑓: 0.0038 ( 96 hom. )

Consequence

DNASE1
NM_005223.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 5.38

Variant links:

Genes affected

DNASE1 (HGNC:2956): (deoxyribonuclease 1) This gene encodes a member of the DNase family. This protein is stored in the zymogen granules of the nuclear envelope and functions by cleaving DNA in an endonucleolytic manner. At least six autosomal codominant alleles have been characterized, DNASE1*1 through DNASE1*6, and the sequence of DNASE1*2 represented in this record. Mutations in this gene have been associated with systemic lupus erythematosus (SLE), an autoimmune disease. A recombinant form of this protein is used to treat the one of the symptoms of cystic fibrosis by hydrolyzing the extracellular DNA in sputum and reducing its viscosity. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

DNASE1 links:

LOC124903631 (HGNC:):

LOC124903631 links:

TRAP1 (HGNC:16264): (TNF receptor associated protein 1) This gene encodes a mitochondrial chaperone protein that is member of the heat shock protein 90 (HSP90) family. The encoded protein has ATPase activity and interacts with tumor necrosis factor type I. This protein may function in regulating cellular stress responses. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

TRAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065968335).

BP6

Variant 16-3656696-G-A is Benign according to our data. Variant chr16-3656696-G-A is described in ClinVar as [Benign]. Clinvar id is 973637.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNASE1	NM_005223.4 linkuse as main transcript	c.379G>A	p.Gly127Arg	missense_variant	5/9	ENST00000246949.10	NP_005214.2
LOC124903631	XR_007064954.1 linkuse as main transcript	n.898C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNASE1	ENST00000246949.10 linkuse as main transcript	c.379G>A	p.Gly127Arg	missense_variant	5/9	1	NM_005223.4	ENSP00000246949	P1	P24855-1

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2987

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0586

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0183

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.00736

AC:

1835

AN:

249262

Hom.:

AF XY:

0.00612

AC XY:

825

AN XY:

134884

show subpopulations

Gnomad AFR exome

AF:

0.0616

Gnomad AMR exome

AF:

0.00810

Gnomad ASJ exome

AF:

0.0183

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00300

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00216

Gnomad OTH exome

AF:

0.00838

GnomAD4 exome

AF:

0.00380

AC:

5555

AN:

1461016

Hom.:

Cov.:

AF XY:

0.00358

AC XY:

2600

AN XY:

726732

show subpopulations

Gnomad4 AFR exome

AF:

0.0630

Gnomad4 AMR exome

AF:

0.00913

Gnomad4 ASJ exome

AF:

0.0186

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00302

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.00152

Gnomad4 OTH exome

AF:

0.00852

GnomAD4 genome

AF:

0.0196

AC:

2985

AN:

152236

Hom.:

Cov.:

AF XY:

0.0195

AC XY:

1451

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0584

Gnomad4 AMR

AF:

0.0183

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.00578

Hom.:

Bravo

AF:

0.0234

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.0619

AC:

272

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00794

AC:

964

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00300

EpiControl

AF:

0.00339

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Systemic lupus erythematosus

Benign:1

Benign, no assertion criteria provided

clinical testing

UOSD Laboratory of Genetics & Genomics of Rare Diseases, Istituto Giannina Gaslini

May 21, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.65

D;D

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.85

.;T

MetaRNN

Benign

0.0066

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Pathogenic

2.9

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Benign

0.28

Sift

Benign

0.035

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.63

MutPred

0.22

Gain of solvent accessibility (P = 0.0014);Gain of solvent accessibility (P = 0.0014);

MVP

0.70

MPC

0.032

ClinPred

0.063

GERP RS

4.3

Varity_R

0.50

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over