Variant 20-57616331-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_030776.3(ZBP1):c.172G>T(p.Val58Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00657 in 1,614,182 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 40 hom. )

Consequence

ZBP1
NM_030776.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.31

Variant links:

Genes affected

ZBP1 (HGNC:16176): (Z-DNA binding protein 1) This gene encodes a Z-DNA binding protein. The encoded protein plays a role in the innate immune response by binding to foreign DNA and inducing type-I interferon production. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ZBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068409443).

BP6

Variant 20-57616331-C-A is Benign according to our data. Variant chr20-57616331-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 779046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBP1	NM_030776.3 linkuse as main transcript	c.172G>T	p.Val58Phe	missense_variant	2/8	ENST00000371173.8	NP_110403.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBP1	ENST00000371173.8 linkuse as main transcript	c.172G>T	p.Val58Phe	missense_variant	2/8	1	NM_030776.3	ENSP00000360215	P2	Q9H171-1

Frequencies

GnomAD3 genomes

AF:

0.00502

AC:

764

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00864

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00490

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00713

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00532

AC:

1339

AN:

251480

Hom.:

AF XY:

0.00575

AC XY:

781

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00387

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00310

Gnomad FIN exome

AF:

0.00545

Gnomad NFE exome

AF:

0.00796

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00673

AC:

9840

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00670

AC XY:

4876

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00445

Gnomad4 ASJ exome

AF:

0.00275

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00315

Gnomad4 FIN exome

AF:

0.00548

Gnomad4 NFE exome

AF:

0.00771

Gnomad4 OTH exome

AF:

0.00584

GnomAD4 genome

AF:

0.00502

AC:

764

AN:

152294

Hom.:

Cov.:

AF XY:

0.00489

AC XY:

364

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00863

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00490

Gnomad4 NFE

AF:

0.00713

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00604

Hom.:

Bravo

AF:

0.00538

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.00536

AC:

651

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00731

EpiControl

AF:

0.00824

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.082

T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.55

T;T

MetaRNN

Benign

0.0068

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.021

D;D

Polyphen

1.0

D;.

Vest4

0.51

MVP

0.64

MPC

0.18

ClinPred

0.035

GERP RS

2.7

Varity_R

0.91

gMVP

0.85

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

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