18-48029377-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001318841.2(ZBTB7C):c.1743C>T(p.Asn581=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,555,300 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (5 hom.)
• Consequence: ZBTB7C NM_001318841.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.218

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 18-48029377-G-A is Benign according to our data. Variant chr18-48029377-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 791653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.218 with no splicing effect.
• BS2: High AC in GnomAd at 235 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB7C	NM_001318841.2	c.1743C>T	p.Asn581=	synonymous_variant	5/5	ENST00000590800.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB7C	ENST00000590800.6	c.1743C>T	p.Asn581=	synonymous_variant	5/5	1	NM_001318841.2	P1
ZBTB7C	ENST00000535628.6	c.1743C>T	p.Asn581=	synonymous_variant	3/3	1		P1
ZBTB7C	ENST00000586438.5	c.1743C>T	p.Asn581=	synonymous_variant	3/3	1		P1
ZBTB7C	ENST00000588982.5	c.1743C>T	p.Asn581=	synonymous_variant	4/4	1		P1

Frequencies

GnomAD3 genomes AF: 0.00155 AC: 235 AN: 152076 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.00623

GnomAD3 exomes AF: 0.00181 AC: 297 AN: 163758 Hom.: 1 AF XY: 0.00192 AC XY: 174 AN XY: 90842

Gnomad AFR exome AF: 0.000963

Gnomad AMR exome AF: 0.00330

Gnomad ASJ exome AF: 0.000821

Gnomad EAS exome AF: 0.0000794

Gnomad SAS exome AF: 0.0000407

Gnomad FIN exome AF: 0.000108

Gnomad NFE exome AF: 0.00258

Gnomad OTH exome AF: 0.00239

GnomAD4 exome AF: 0.00207 AC: 2898 AN: 1403112 Hom.: 5 Cov.: 32 AF XY: 0.00208 AC XY: 1447 AN XY: 694822

Gnomad4 AFR exome AF: 0.000664

Gnomad4 AMR exome AF: 0.00362

Gnomad4 ASJ exome AF: 0.000635

Gnomad4 EAS exome AF: 0.0000550

Gnomad4 SAS exome AF: 0.0000123

Gnomad4 FIN exome AF: 0.000129

Gnomad4 NFE exome AF: 0.00237

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.00154 AC: 235 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.00140 AC XY: 104 AN XY: 74400

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00360

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00210

Gnomad4 OTH AF: 0.00617

Alfa AF: 0.00142 Hom.: 0

Bravo AF: 0.00194

Asia WGS AF: 0.000579 AC: 2 AN: 3468

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	May 21, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	ZBTB7C: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	8.5
Dann	Benign	0.61

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: rs186779400; hg19: chr18-45555748; COSMIC: COSV59689750;