dbSNP rs34863160: ZNF470:p.Lys680Glu (chr19-56578467-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001001668.4(ZNF470):c.2038A>G(p.Lys680Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,612,548 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.011 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 27 hom. )

Consequence

ZNF470
NM_001001668.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.10

Publications

11 publications found

Variant links:

Genes affected

ZNF470 (HGNC:22220): (zinc finger protein 470) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ZNF470 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=0.0017959774).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.011 (1668/152278) while in subpopulation AFR AF = 0.0381 (1583/41562). AF 95% confidence interval is 0.0365. There are 26 homozygotes in GnomAd4. There are 771 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF470	NM_001001668.4 link	c.2038A>G	p.Lys680Glu	missense_variant	Exon 6 of 6	ENST00000330619.13	NP_001001668.3	Q6ECI4-1
ZNF470	XM_047438804.1 link	c.2038A>G	p.Lys680Glu	missense_variant	Exon 7 of 7		XP_047294760.1
ZNF470	XM_047438805.1 link	c.1885A>G	p.Lys629Glu	missense_variant	Exon 5 of 5		XP_047294761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF470	ENST00000330619.13 link	c.2038A>G	p.Lys680Glu	missense_variant	Exon 6 of 6	1	NM_001001668.4	ENSP00000333223.7		Q6ECI4-1

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1665

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0381

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00296

AC:

738

AN:

249120

AF XY:

0.00215

show subpopulations

Gnomad AFR exome

AF:

0.0383

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00315

GnomAD4 exome

AF:

0.00124

AC:

1806

AN:

1460270

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

771

AN XY:

726488

show subpopulations

African (AFR)

AF:

0.0416

AC:

1389

AN:

33398

American (AMR)

AF:

0.00263

AC:

117

AN:

44444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25978

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.000139

AC:

AN:

86130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000131

AC:

146

AN:

1111270

Other (OTH)

AF:

0.00222

AC:

134

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

104

208

313

417

521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.0110

AC:

1668

AN:

152278

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

771

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0381

AC:

1583

AN:

41562

American (AMR)

AF:

0.00418

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68012

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

173

259

346

432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00433

Hom.:

Bravo

AF:

0.0124

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0379

AC:

167

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00359

AC:

436

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0052

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.031

.;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.33

N;N

PhyloP100

-2.1

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.010

Sift

Benign

0.17

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.0010

B;B

Vest4

0.13

MVP

0.16

MPC

0.014

ClinPred

0.0031

GERP RS

1.9

Varity_R

0.10

gMVP

0.018

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

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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