Variant chr1-15943899-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003443.3(ZBTB17):c.1372-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000915 in 1,591,998 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 11 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 6 hom. )

Consequence

ZBTB17
NM_003443.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00007091

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.20

Variant links:

Genes affected

ZBTB17 (HGNC:12936): (zinc finger and BTB domain containing 17) This gene encodes a zinc finger protein involved in the regulation of c-myc. The symbol MIZ1 has also been associated with PIAS2 which is a different gene located on chromosome 18. [provided by RefSeq, Jul 2008]

ZBTB17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 1-15943899-T-C is Benign according to our data. Variant chr1-15943899-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3056701.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00472 (718/152096) while in subpopulation AFR AF= 0.0164 (680/41488). AF 95% confidence interval is 0.0154. There are 11 homozygotes in gnomad4. There are 323 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 718 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB17	NM_003443.3 linkuse as main transcript	c.1372-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000375743.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB17	ENST00000375743.9 linkuse as main transcript	c.1372-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003443.3	P2	Q13105-1

Frequencies

GnomAD3 genomes

AF:

0.00472

AC:

717

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000959

AC:

199

AN:

207496

Hom.:

AF XY:

0.000684

AC XY:

AN XY:

112566

show subpopulations

Gnomad AFR exome

AF:

0.0144

Gnomad AMR exome

AF:

0.000464

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000221

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000513

AC:

738

AN:

1439902

Hom.:

Cov.:

AF XY:

0.000441

AC XY:

315

AN XY:

714504

show subpopulations

Gnomad4 AFR exome

AF:

0.0187

Gnomad4 AMR exome

AF:

0.000553

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000227

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00472

AC:

718

AN:

152096

Hom.:

Cov.:

AF XY:

0.00434

AC XY:

323

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0164

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00252

Hom.:

Bravo

AF:

0.00536

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ZBTB17-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 20, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.1

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000071

dbscSNV1_RF

Benign

0.050

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over