dbSNP rs10016022: ZNF518B:p.Asp349Asp (chr4-10445282-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_053042.3(ZNF518B):c.1047T>C(p.Asp349Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 1,614,078 control chromosomes in the GnomAD database, including 447,782 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.77 ( 45688 hom., cov: 33)

Exomes 𝑓: 0.74 ( 402094 hom. )

Consequence

ZNF518B
NM_053042.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.52

Publications

22 publications found

Variant links:

Genes affected

ZNF518B (HGNC:29365): (zinc finger protein 518B) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF518B Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ZNF518B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP7

Synonymous conserved (PhyloP=-3.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF518B	NM_053042.3 link	c.1047T>C	p.Asp349Asp	synonymous_variant	Exon 3 of 3	ENST00000326756.4	NP_444270.2	Q9C0D4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF518B	ENST00000326756.4 link	c.1047T>C	p.Asp349Asp	synonymous_variant	Exon 3 of 3	3	NM_053042.3	ENSP00000317614.3		Q9C0D4

Frequencies

GnomAD3 genomes

AF:

0.772

AC:

117368

AN:

152090

Hom.:

45633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.869

Gnomad AMI

AF:

0.694

Gnomad AMR

AF:

0.723

Gnomad ASJ

AF:

0.739

Gnomad EAS

AF:

0.809

Gnomad SAS

AF:

0.766

Gnomad FIN

AF:

0.682

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.737

Gnomad OTH

AF:

0.782

GnomAD2 exomes

AF:

0.744

AC:

186970

AN:

251338

AF XY:

0.745

show subpopulations

Gnomad AFR exome

AF:

0.872

Gnomad AMR exome

AF:

0.674

Gnomad ASJ exome

AF:

0.746

Gnomad EAS exome

AF:

0.811

Gnomad FIN exome

AF:

0.676

Gnomad NFE exome

AF:

0.739

Gnomad OTH exome

AF:

0.743

GnomAD4 exome

AF:

0.741

AC:

1082818

AN:

1461870

Hom.:

402094

Cov.:

AF XY:

0.742

AC XY:

539379

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.880

AC:

29451

AN:

33480

American (AMR)

AF:

0.677

AC:

30283

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.746

AC:

19503

AN:

26136

East Asian (EAS)

AF:

0.795

AC:

31578

AN:

39698

South Asian (SAS)

AF:

0.774

AC:

66783

AN:

86256

European-Finnish (FIN)

AF:

0.685

AC:

36586

AN:

53416

Middle Eastern (MID)

AF:

0.778

AC:

4485

AN:

5768

European-Non Finnish (NFE)

AF:

0.736

AC:

818703

AN:

1111996

Other (OTH)

AF:

0.752

AC:

45446

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

18656

37312

55967

74623

93279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20176

40352

60528

80704

100880

<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:

0.772

AC:

117486

AN:

152208

Hom.:

45688

Cov.:

AF XY:

0.768

AC XY:

57176

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.869

AC:

36103

AN:

41544

American (AMR)

AF:

0.724

AC:

11066

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.739

AC:

2567

AN:

3472

East Asian (EAS)

AF:

0.810

AC:

4195

AN:

5180

South Asian (SAS)

AF:

0.765

AC:

3692

AN:

4826

European-Finnish (FIN)

AF:

0.682

AC:

7201

AN:

10564

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.737

AC:

50157

AN:

68016

Other (OTH)

AF:

0.785

AC:

1658

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1363

2725

4088

5450

6813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<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:

0.748

Hom.:

187171

Bravo

AF:

0.778

Asia WGS

AF:

0.806

AC:

2806

AN:

3478

EpiCase

AF:

0.738

EpiControl

AF:

0.745

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.22

(source)

DANN

Benign

0.42

PhyloP100

-3.5

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over