Genetic Variant ZBTB1:c.*1423A>C (chr14-64533320-A-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_014950.3(ZBTB1):c.*1423A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,108 control chromosomes in the GnomAD database, including 20,076 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 0.51 ( 20012 hom., cov: 31)

Exomes 𝑓: 0.64 ( 64 hom. )

Consequence

ZBTB1
NM_014950.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.368

Publications

17 publications found

Variant links:

Genes affected

ZBTB1 (HGNC:20259): (zinc finger and BTB domain containing 1) Enables K63-linked polyubiquitin modification-dependent protein binding activity; protein heterodimerization activity; and protein homodimerization activity. Involved in several processes, including cellular response to UV; nucleobase-containing compound biosynthetic process; and protein homooligomerization. Located in centrosome; nuclear body; and nuclear membrane. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB1 links:

HSPA2-AS1 (HGNC:55433): (HSPA2 and ZBTB1 antisense RNA 1)

HSPA2-AS1 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014950.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB1	NM_014950.3		c.*1423A>C		3_prime_UTR	Exon 3 of 3	NP_055765.2	Q9Y2K1-2
	HSPA2-AS1	NR_110550.1		n.53-751T>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZBTB1	ENST00000358738.3	TSL:1	c.*1423A>C	3_prime_UTR	Exon 3 of 3	ENSP00000351587.3	Q9Y2K1-2
HSPA2-AS1	ENST00000554918.1	TSL:3	n.53-751T>G	intron	N/A
HSPA2-AS1	ENST00000648003.1		n.475-751T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77275

AN:

151692

Hom.:

19997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.493

Gnomad AMI

AF:

0.602

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.655

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.612

Gnomad MID

AF:

0.429

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.485

GnomAD4 exome

AF:

0.644

AC:

192

AN:

298

Hom.:

Cov.:

AF XY:

0.642

AC XY:

122

AN XY:

190

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.646

AC:

190

AN:

294

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.509

AC:

77330

AN:

151810

Hom.:

20012

Cov.:

AF XY:

0.518

AC XY:

38447

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.493

AC:

20444

AN:

41436

American (AMR)

AF:

0.582

AC:

8877

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1554

AN:

3468

East Asian (EAS)

AF:

0.655

AC:

3387

AN:

5170

South Asian (SAS)

AF:

0.567

AC:

2725

AN:

4808

European-Finnish (FIN)

AF:

0.612

AC:

6454

AN:

10544

Middle Eastern (MID)

AF:

0.431

AC:

124

AN:

288

European-Non Finnish (NFE)

AF:

0.475

AC:

32193

AN:

67842

Other (OTH)

AF:

0.488

AC:

1027

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1933

3866

5800

7733

9666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<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:

0.481

Hom.:

13303

Bravo

AF:

0.507

Asia WGS

AF:

0.570

AC:

1970

AN:

3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.60

(source)

DANN

Benign

0.62

PhyloP100

0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over