19-57353714-T-C

Variant names:

• chr19-57353714-T-C
• rs862703
• NM_020657.4:c.34-11T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020657.4(ZNF304):​c.34-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 1,604,544 control chromosomes in the GnomAD database, including 438,697 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 0.70 (37604 hom., cov: 29)
  • Exomes 𝑓: 0.74 (401093 hom.)
• Consequence: ZNF304 NM_020657.4 intron
• Scores: Splicing: ADA: 0.00007502
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 28 publications found

Genes affected

ZNF304 (HGNC:13505): (zinc finger protein 304) This gene encodes a member of the Krueppel C2H2-type zinc-finger family of proteins. The encoded protein functions as a transcriptional repressor that recruits a corepressor complex to stimulate promoter hypermethylation and transcriptional silencing of target genes. Expression of this gene is upregulated in colorectal, ovarian and breast cancer, and this gene may promote cancer cell survival, growth and invasion. [provided by RefSeq, Jul 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF304	NM_020657.4	c.34-11T>C		intron_variant	Intron 1 of 2	ENST00000282286.6	NP_065708.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF304	ENST00000282286.6	c.34-11T>C		intron_variant	Intron 1 of 2	2	NM_020657.4	ENSP00000282286.4
ZNF304	ENST00000443917.6	c.34-11T>C		intron_variant	Intron 1 of 3	1		ENSP00000401642.2
ZNF304	ENST00000598744.1	c.-93-11T>C		intron_variant	Intron 2 of 3	1		ENSP00000470319.1
ZNF304	ENST00000391705.7	c.34-11T>C		intron_variant	Intron 2 of 3	5		ENSP00000375586.3

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105711 AN: 151700 Hom.: 37577 Cov.: 29

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.722

GnomAD2 exomes AF: 0.758 AC: 184339 AN: 243270 AF XY: 0.768

Gnomad AFR exome AF: 0.572

Gnomad AMR exome AF: 0.782

Gnomad ASJ exome AF: 0.706

Gnomad EAS exome AF: 0.955

Gnomad FIN exome AF: 0.671

Gnomad NFE exome AF: 0.725

Gnomad OTH exome AF: 0.750

GnomAD4 exome AF: 0.740 AC: 1075052 AN: 1452726 Hom.: 401093 Cov.: 48 AF XY: 0.745 AC XY: 538365 AN XY: 722256

African (AFR) AF: 0.576 AC: 19165 AN: 33276

American (AMR) AF: 0.780 AC: 34207 AN: 43846

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 17847 AN: 25392

East Asian (EAS) AF: 0.953 AC: 37730 AN: 39590

South Asian (SAS) AF: 0.914 AC: 77246 AN: 84498

European-Finnish (FIN) AF: 0.676 AC: 35811 AN: 52992

Middle Eastern (MID) AF: 0.800 AC: 4578 AN: 5724

European-Non Finnish (NFE) AF: 0.726 AC: 803595 AN: 1107380

Other (OTH) AF: 0.748 AC: 44873 AN: 60028

GnomAD4 genome AF: 0.697 AC: 105780 AN: 151818 Hom.: 37604 Cov.: 29 AF XY: 0.701 AC XY: 51941 AN XY: 74136

African (AFR) AF: 0.578 AC: 23884 AN: 41348

American (AMR) AF: 0.776 AC: 11847 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2389 AN: 3466

East Asian (EAS) AF: 0.949 AC: 4886 AN: 5148

South Asian (SAS) AF: 0.921 AC: 4424 AN: 4802

European-Finnish (FIN) AF: 0.674 AC: 7101 AN: 10542

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48871 AN: 67930

Other (OTH) AF: 0.723 AC: 1521 AN: 2104

Alfa AF: 0.707 Hom.: 16787

Bravo AF: 0.695

Asia WGS AF: 0.891 AC: 3098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.1
DANN	Benign	0.39
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000075
dbscSNV1_RF	Benign	0.036
SpliceAI score (max)		0.080		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: rs862703; hg19: chr19-57865082;