rs848217

Variant names:

• chr1-15945755-A-G
• rs848217
• NM_003443.3:c.621T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003443.3(ZBTB17):​c.621T>C​(p.Ala207Ala) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.811
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -21 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 VariationId is 1264129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ZBTB17	NM_003443.3	c.621T>C	p.Ala207Ala	synonymous_variant	Exon 6 of 16	ENST00000375743.9	NP_003434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB17	ENST00000375743.9	c.621T>C	p.Ala207Ala	synonymous_variant	Exon 6 of 16	1	NM_003443.3	ENSP00000364895.4

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

GnomAD2 exomes AF: 0.530 AC: 128442 AN: 242426 AF XY: 0.528

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 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

African (AFR) AF: 0.469 AC: 15682 AN: 33468

American (AMR) AF: 0.688 AC: 30710 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 15127 AN: 26064

East Asian (EAS) AF: 0.323 AC: 12827 AN: 39686

South Asian (SAS) AF: 0.581 AC: 50098 AN: 86168

European-Finnish (FIN) AF: 0.530 AC: 24402 AN: 46080

Middle Eastern (MID) AF: 0.532 AC: 3062 AN: 5758

European-Non Finnish (NFE) AF: 0.498 AC: 553075 AN: 1111604

Other (OTH) AF: 0.499 AC: 30057 AN: 60278

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

African (AFR) AF: 0.474 AC: 19621 AN: 41432

American (AMR) AF: 0.609 AC: 9310 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2043 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1560 AN: 5148

South Asian (SAS) AF: 0.575 AC: 2775 AN: 4826

European-Finnish (FIN) AF: 0.546 AC: 5772 AN: 10570

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33695 AN: 67892

Other (OTH) AF: 0.486 AC: 1025 AN: 2108

Alfa AF: 0.504 Hom.: 7253

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.35
PhyloP100		-0.81
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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