rs848217

Positions:

• chr1-15945755-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_003443.3(ZBTB17):​c.621T>C​(p.Ala207=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,605,680 control chromosomes in the GnomAD database, including 207,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19516 hom., cov: 32)
  • Exomes 𝑓: 0.51 (187960 hom.)
• Consequence: ZBTB17 NM_003443.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.811

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-15945755-A-G is Benign according to our data. Variant chr1-15945755-A-G is described in ClinVar as [Benign]. Clinvar id is 1264129.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.811 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB17	NM_003443.3	c.621T>C	p.Ala207=	synonymous_variant	6/16	ENST00000375743.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB17	ENST00000375743.9	c.621T>C	p.Ala207=	synonymous_variant	6/16	1	NM_003443.3	P2

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76316 AN: 151820 Hom.: 19480 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.482

GnomAD3 exomes AF: 0.530 AC: 128442 AN: 242426 Hom.: 35251 AF XY: 0.528 AC XY: 69776 AN XY: 132188

Gnomad AFR exome AF: 0.469

Gnomad AMR exome AF: 0.700

Gnomad ASJ exome AF: 0.584

Gnomad EAS exome AF: 0.329

Gnomad SAS exome AF: 0.582

Gnomad FIN exome AF: 0.528

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.526

GnomAD4 exome AF: 0.506 AC: 735040 AN: 1453742 Hom.: 187960 Cov.: 70 AF XY: 0.508 AC XY: 367455 AN XY: 723584

Gnomad4 AFR exome AF: 0.469

Gnomad4 AMR exome AF: 0.688

Gnomad4 ASJ exome AF: 0.580

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.581

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.498

Gnomad4 OTH exome AF: 0.499

GnomAD4 genome AF: 0.503 AC: 76406 AN: 151938 Hom.: 19516 Cov.: 32 AF XY: 0.509 AC XY: 37784 AN XY: 74276

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.486

Alfa AF: 0.505 Hom.: 7163

Bravo AF: 0.505

Asia WGS AF: 0.511 AC: 1776 AN: 3478

EpiCase AF: 0.502

EpiControl AF: 0.502

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.35

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

LitVar

Other links and lift over

dbSNP: rs848217; hg19: chr1-16272250; COSMIC: COSV65268244; COSMIC: COSV65268244;