20-57615578-C-T

Position:

• chr20-57615578-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030776.3(ZBP1):​c.262G>A​(p.Glu88Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 1,611,400 control chromosomes in the GnomAD database, including 379,339 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.59 (28621 hom., cov: 31)
  • Exomes 𝑓: 0.69 (350718 hom.)
• Consequence: ZBP1 NM_030776.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.3352924E-7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBP1	NM_030776.3	c.262G>A	p.Glu88Lys	missense_variant, splice_region_variant	3/8	ENST00000371173.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBP1	ENST00000371173.8	c.262G>A	p.Glu88Lys	missense_variant, splice_region_variant	3/8	1	NM_030776.3	P2

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89188 AN: 151718 Hom.: 28612 Cov.: 31

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.604

GnomAD3 exomes AF: 0.691 AC: 172458 AN: 249400 Hom.: 61514 AF XY: 0.703 AC XY: 94797 AN XY: 134932

Gnomad AFR exome AF: 0.295

Gnomad AMR exome AF: 0.754

Gnomad ASJ exome AF: 0.615

Gnomad EAS exome AF: 0.737

Gnomad SAS exome AF: 0.836

Gnomad FIN exome AF: 0.694

Gnomad NFE exome AF: 0.690

Gnomad OTH exome AF: 0.676

GnomAD4 exome AF: 0.689 AC: 1005490 AN: 1459566 Hom.: 350718 Cov.: 47 AF XY: 0.694 AC XY: 503823 AN XY: 726176

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.747

Gnomad4 ASJ exome AF: 0.612

Gnomad4 EAS exome AF: 0.707

Gnomad4 SAS exome AF: 0.836

Gnomad4 FIN exome AF: 0.690

Gnomad4 NFE exome AF: 0.689

Gnomad4 OTH exome AF: 0.672

GnomAD4 genome AF: 0.588 AC: 89218 AN: 151834 Hom.: 28621 Cov.: 31 AF XY: 0.596 AC XY: 44186 AN XY: 74194

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.606

Alfa AF: 0.660 Hom.: 46626

Bravo AF: 0.571

TwinsUK AF: 0.689 AC: 2554

ALSPAC AF: 0.687 AC: 2649

ESP6500AA AF: 0.312 AC: 1373

ESP6500EA AF: 0.684 AC: 5886

ExAC AF: 0.686 AC: 83251

Asia WGS AF: 0.732 AC: 2547 AN: 3478

EpiCase AF: 0.693

EpiControl AF: 0.682

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.3
DANN	Benign	0.73
DEOGEN2	Benign	0.0045	T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.47	T;T;T
MetaRNN	Benign	9.3e-7	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.060	N;.;N
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.31	T;T;T
Polyphen		0.0060	B;.;.
Vest4		0.021
MPC		0.049
ClinPred		0.0068	T
GERP RS		-1.1
Varity_R		0.028
gMVP		0.44

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

Other links and lift over

dbSNP: rs2073145; hg19: chr20-56190634;