Genetic Variant ZNF304:c.34-11T>C (chr19-57353714-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Variant links:

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]

ZNF304 links:

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ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020657.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF304	NM_020657.4	MANE Select	c.34-11T>C	intron	N/A	NP_065708.2	Q9HCX3
ZNF304	NM_001290318.2		c.34-11T>C	intron	N/A	NP_001277247.1	E7EQD3
ZNF304	NM_001290319.2		c.-93-11T>C	intron	N/A	NP_001277248.1	M0QZ59

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF304	ENST00000282286.6	TSL:2 MANE Select	c.34-11T>C	intron	N/A	ENSP00000282286.4	Q9HCX3
ZNF304	ENST00000443917.6	TSL:1	c.34-11T>C	intron	N/A	ENSP00000401642.2	E7EQD3
ZNF304	ENST00000598744.1	TSL:1	c.-93-11T>C	intron	N/A	ENSP00000470319.1	M0QZ59

Frequencies

GnomAD3 genomes

AF:

0.697

AC:

105711

AN:

151700

Hom.:

37577

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.745

AC XY:

538365

AN XY:

722256

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

13280

26560

39841

53121

66401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20072

40144

60216

80288

100360

<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:

0.697

AC:

105780

AN:

151818

Hom.:

37604

Cov.:

AF XY:

0.701

AC XY:

51941

AN XY:

74136

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1548

3096

4643

6191

7739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<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:

0.707

Hom.:

16787

Bravo

AF:

0.695

Asia WGS

AF:

0.891

AC:

3098

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

5.1

(source)

DANN

Benign

0.39

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over