Genetic Variant ZNF804B:p.Cys248Tyr (chr7-89333725-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181646.5(ZNF804B):c.743G>A(p.Cys248Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 1,613,456 control chromosomes in the GnomAD database, including 7,354 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.041 ( 754 hom., cov: 32)

Exomes 𝑓: 0.034 ( 6600 hom. )

Consequence

ZNF804B
NM_181646.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.79

Publications

12 publications found

Variant links:

Genes affected

ZNF804B (HGNC:21958): (zinc finger protein 804B) Predicted to enable metal ion binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF804B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.710853E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF804B	NM_181646.5 link	c.743G>A	p.Cys248Tyr	missense_variant	Exon 4 of 4	ENST00000333190.5	NP_857597.1	A4D1E1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF804B	ENST00000333190.5 link	c.743G>A	p.Cys248Tyr	missense_variant	Exon 4 of 4	1	NM_181646.5	ENSP00000329638.4		A4D1E1
ZNF804B	ENST00000611114.1 link	c.494G>A	p.Cys165Tyr	missense_variant	Exon 3 of 3	5		ENSP00000478506.1		A0A087WUA7

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6305

AN:

151964

Hom.:

753

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.463

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00603

Gnomad OTH

AF:

0.0431

GnomAD2 exomes

AF:

0.0882

AC:

22034

AN:

249928

AF XY:

0.0817

show subpopulations

Gnomad AFR exome

AF:

0.0200

Gnomad AMR exome

AF:

0.228

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.457

Gnomad FIN exome

AF:

0.0117

Gnomad NFE exome

AF:

0.00560

Gnomad OTH exome

AF:

0.0567

GnomAD4 exome

AF:

0.0340

AC:

49700

AN:

1461374

Hom.:

6600

Cov.:

AF XY:

0.0358

AC XY:

26036

AN XY:

726980

show subpopulations

African (AFR)

AF:

0.0189

AC:

632

AN:

33450

American (AMR)

AF:

0.212

AC:

9470

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.0120

AC:

314

AN:

26110

East Asian (EAS)

AF:

0.455

AC:

18057

AN:

39688

South Asian (SAS)

AF:

0.133

AC:

11492

AN:

86238

European-Finnish (FIN)

AF:

0.0112

AC:

596

AN:

53366

Middle Eastern (MID)

AF:

0.0118

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00549

AC:

6104

AN:

1111758

Other (OTH)

AF:

0.0491

AC:

2967

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

2417

4833

7250

9666

12083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

688

1376

2064

2752

3440

<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:

0.0415

AC:

6309

AN:

152082

Hom.:

754

Cov.:

AF XY:

0.0466

AC XY:

3465

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0191

AC:

794

AN:

41532

American (AMR)

AF:

0.112

AC:

1704

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

AN:

3466

East Asian (EAS)

AF:

0.463

AC:

2380

AN:

5136

South Asian (SAS)

AF:

0.154

AC:

743

AN:

4822

European-Finnish (FIN)

AF:

0.0132

AC:

140

AN:

10588

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00603

AC:

410

AN:

67974

Other (OTH)

AF:

0.0451

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

239

478

718

957

1196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0271

Hom.:

2227

Bravo

AF:

0.0510

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.0184

AC:

ESP6500EA

AF:

0.00628

AC:

ExAC

AF:

0.0817

AC:

9918

Asia WGS

AF:

0.300

AC:

1040

AN:

3478

EpiCase

AF:

0.00551

EpiControl

AF:

0.00481

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.00047

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.2

M;.

PhyloP100

2.8

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.0

D;.

REVEL

Benign

0.057

Sift

Benign

0.16

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.22

B;.

Vest4

0.055

MPC

0.058

ClinPred

0.030

GERP RS

4.2

Varity_R

0.12

gMVP

0.11

Mutation Taster

=99/1

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