dbSNP rs3853894: ZBTB4:c.-39C>T (chr17-7467286-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_001128833.2(ZBTB4):c.-39C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 983,610 control chromosomes in the GnomAD database, including 11,427 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 0.17 ( 2379 hom., cov: 32)

Exomes 𝑓: 0.15 ( 9048 hom. )

Consequence

ZBTB4
NM_001128833.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0300

Publications

17 publications found

Variant links:

Genes affected

ZBTB4 (HGNC:23847): (zinc finger and BTB domain containing 4) Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; methyl-CpNpG binding activity; and sequence-specific DNA binding activity. Involved in cellular response to DNA damage stimulus and negative regulation of transcription by RNA polymerase II. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB4 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 (BayesDel_noAF=-0.64).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB4	NM_001128833.2 link	c.-39C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 4	ENST00000380599.9	NP_001122305.1
ZBTB4	NM_001128833.2 link	c.-39C>T		5_prime_UTR_variant	Exon 2 of 4	ENST00000380599.9	NP_001122305.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ZBTB4	ENST00000380599.9 link	c.-39C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 4	1	NM_001128833.2	ENSP00000369973.4
ZBTB4	ENST00000311403.4 link	c.-39C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 4	1		ENSP00000307858.4
ZBTB4	ENST00000380599.9 link	c.-39C>T	5_prime_UTR_variant	Exon 2 of 4	1	NM_001128833.2	ENSP00000369973.4
ZBTB4	ENST00000311403.4 link	c.-39C>T	5_prime_UTR_variant	Exon 2 of 4	1		ENSP00000307858.4

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25116

AN:

151984

Hom.:

2363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.0994

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.149

GnomAD4 exome

AF:

0.145

AC:

120953

AN:

831508

Hom.:

9048

Cov.:

AF XY:

0.146

AC XY:

55933

AN XY:

384260

show subpopulations

African (AFR)

AF:

0.127

AC:

2000

AN:

15794

American (AMR)

AF:

0.233

AC:

253

AN:

1086

Ashkenazi Jewish (ASJ)

AF:

0.0940

AC:

492

AN:

5232

East Asian (EAS)

AF:

0.203

AC:

755

AN:

3726

South Asian (SAS)

AF:

0.224

AC:

3672

AN:

16414

European-Finnish (FIN)

AF:

0.279

AC:

223

AN:

800

Middle Eastern (MID)

AF:

0.0818

AC:

133

AN:

1626

European-Non Finnish (NFE)

AF:

0.144

AC:

109176

AN:

759498

Other (OTH)

AF:

0.155

AC:

4249

AN:

27332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

5214

10428

15641

20855

26069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5412

10824

16236

21648

27060

<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:

0.165

AC:

25148

AN:

152102

Hom.:

2379

Cov.:

AF XY:

0.174

AC XY:

12968

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.138

AC:

5735

AN:

41518

American (AMR)

AF:

0.198

AC:

3021

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0994

AC:

344

AN:

3462

East Asian (EAS)

AF:

0.213

AC:

1098

AN:

5160

South Asian (SAS)

AF:

0.219

AC:

1054

AN:

4816

European-Finnish (FIN)

AF:

0.310

AC:

3277

AN:

10558

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.149

AC:

10134

AN:

67988

Other (OTH)

AF:

0.157

AC:

331

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1083

2166

3249

4332

5415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<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:

0.146

Hom.:

6746

Bravo

AF:

0.154

Asia WGS

AF:

0.281

AC:

976

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.030

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

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