18-48029458-T-C

Variant summary

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

The NM_001318841.2(ZBTB7C):c.1662A>G(p.Thr554=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,595,514 control chromosomes in the GnomAD database, including 77,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (10693 hom., cov: 34)
  • Exomes 𝑓: 0.30 (67188 hom.)
• Consequence: ZBTB7C NM_001318841.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

Genes affected

ZBTB7C (HGNC:31700): (zinc finger and BTB domain containing 7C) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of cell population proliferation. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 18-48029458-T-C is Benign according to our data. Variant chr18-48029458-T-C is described in ClinVar as [Benign]. Clinvar id is 1270372.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB7C	NM_001318841.2	c.1662A>G	p.Thr554=	synonymous_variant	5/5	ENST00000590800.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB7C	ENST00000590800.6	c.1662A>G	p.Thr554=	synonymous_variant	5/5	1	NM_001318841.2	P1
ZBTB7C	ENST00000535628.6	c.1662A>G	p.Thr554=	synonymous_variant	3/3	1		P1
ZBTB7C	ENST00000586438.5	c.1662A>G	p.Thr554=	synonymous_variant	3/3	1		P1
ZBTB7C	ENST00000588982.5	c.1662A>G	p.Thr554=	synonymous_variant	4/4	1		P1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54760 AN: 151966 Hom.: 10666 Cov.: 34

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.329

GnomAD3 exomes AF: 0.333 AC: 74055 AN: 222526 Hom.: 13073 AF XY: 0.323 AC XY: 39728 AN XY: 123124

Gnomad AFR exome AF: 0.496

Gnomad AMR exome AF: 0.434

Gnomad ASJ exome AF: 0.286

Gnomad EAS exome AF: 0.465

Gnomad SAS exome AF: 0.331

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.301

GnomAD4 exome AF: 0.300 AC: 433023 AN: 1443438 Hom.: 67188 Cov.: 34 AF XY: 0.299 AC XY: 214882 AN XY: 718110

Gnomad4 AFR exome AF: 0.519

Gnomad4 AMR exome AF: 0.429

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.432

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.289

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.316

GnomAD4 genome AF: 0.361 AC: 54835 AN: 152076 Hom.: 10693 Cov.: 34 AF XY: 0.362 AC XY: 26886 AN XY: 74362

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.333

Alfa AF: 0.296 Hom.: 2743

Bravo AF: 0.377

Asia WGS AF: 0.428 AC: 1464 AN: 3426

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

Nov 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	3.9
Dann	Benign	0.54

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: rs7231151; hg19: chr18-45555829; COSMIC: COSV59688124;