19-56578467-A-G

Variant names:

• chr19-56578467-A-G
• rs34863160
• NM_001001668.4:c.2038A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• Publications: 11 publications found

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]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001668.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF470	NM_001001668.4	MANE Select	c.2038A>G	p.Lys680Glu	missense	Exon 6 of 6	NP_001001668.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF470	ENST00000330619.13	TSL:1 MANE Select	c.2038A>G	p.Lys680Glu	missense	Exon 6 of 6	ENSP00000333223.7
	ZNF470	ENST00000601902.5	TSL:1	c.283+3734A>G		intron	N/A	ENSP00000471379.1
	ZNF470	ENST00000391709.4	TSL:5	c.2038A>G	p.Lys680Glu	missense	Exon 4 of 4	ENSP00000375590.3

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1665 AN: 152160 Hom.: 25 Cov.: 32

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

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.: 27 Cov.: 33 AF XY: 0.00106 AC XY: 771 AN XY: 726488

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: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5756

European-Non Finnish (NFE) AF: 0.000131 AC: 146 AN: 1111270

Other (OTH) AF: 0.00222 AC: 134 AN: 60290

GnomAD4 genome AF: 0.0110 AC: 1668 AN: 152278 Hom.: 26 Cov.: 32 AF XY: 0.0104 AC XY: 771 AN XY: 74462

African (AFR) AF: 0.0381 AC: 1583 AN: 41562

American (AMR) AF: 0.00418 AC: 64 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68012

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00433 Hom.: 27

Bravo AF: 0.0124

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0379 AC: 167

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00359 AC: 436

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.031	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.33	N
PhyloP100		-2.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.010
Sift	Benign	0.17	T
Sift4G	Benign	0.19	T
Polyphen		0.0010	B
Vest4		0.13
MVP		0.16
MPC		0.014
ClinPred		0.0031	T
GERP RS		1.9
Varity_R		0.10
gMVP		0.018
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34863160; hg19: chr19-57089835;