dbSNP rs1542313: 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 ENST00000358738.3(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
ENST00000358738.3 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:

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=-0.89).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
ZBTB1	NM_014950.3 link	c.*1423A>C	3_prime_UTR_variant	Exon 3 of 3	NP_055765.2	Q9Y2K1-2
ZBTB1	XM_047431107.1 link	c.*1423A>C	3_prime_UTR_variant	Exon 6 of 6	XP_047287063.1
ZBTB1	XM_047431108.1 link	c.*1423A>C	3_prime_UTR_variant	Exon 6 of 6	XP_047287064.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ZBTB1	ENST00000358738.3 link	c.*1423A>C	3_prime_UTR_variant	Exon 3 of 3	1	ENSP00000351587.3	Q9Y2K1-2
HSPA2-AS1	ENST00000554918.1 link	n.53-751T>G	intron_variant	Intron 1 of 3	3
HSPA2-AS1	ENST00000648003.1 link	n.475-751T>G	intron_variant	Intron 1 of 3

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over