Genetic Variant ZBTB7B:p.Thr211Thr (chr1-155015293-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001256455.2(ZBTB7B):c.633C>T(p.Thr211Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000449 in 1,612,782 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 2 hom. )

Consequence

ZBTB7B
NM_001256455.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.65

Variant links:

Genes affected

ZBTB7B (HGNC:18668): (zinc finger and BTB domain containing 7B) This gene encodes a zinc finger-containing transcription factor that acts as a key regulator of lineage commitment of immature T-cell precursors. It is necessary and sufficient for commitment of CD4 lineage, while its absence causes CD8 commitment. It also functions as a transcriptional repressor of type I collagen genes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

ZBTB7B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 1-155015293-C-T is Benign according to our data. Variant chr1-155015293-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639388.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.65 with no splicing effect.

BS2

High AC in GnomAd4 at 110 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB7B	NM_001256455.2 link	c.633C>T	p.Thr211Thr	synonymous_variant	Exon 2 of 3	ENST00000535420.6	NP_001243384.1	O15156-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZBTB7B	ENST00000535420.6 link	c.633C>T	p.Thr211Thr	synonymous_variant	Exon 2 of 3	5	NM_001256455.2	ENSP00000438647.1	O15156-1
ZBTB7B	ENST00000292176.2 link	c.633C>T	p.Thr211Thr	synonymous_variant	Exon 1 of 2	1		ENSP00000292176.2	O15156-1
ZBTB7B	ENST00000368426.3 link	c.633C>T	p.Thr211Thr	synonymous_variant	Exon 3 of 4	1		ENSP00000357411.3	O15156-1
ZBTB7B	ENST00000417934.6 link	c.735C>T	p.Thr245Thr	synonymous_variant	Exon 4 of 5	2		ENSP00000406286.2	O15156-2

Frequencies

GnomAD3 genomes

AF:

0.000723

AC:

110

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

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:

0.000588

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000278

AC:

AN:

248460

Hom.:

AF XY:

0.000267

AC XY:

AN XY:

134684

show subpopulations

Gnomad AFR exome

AF:

0.000189

Gnomad AMR exome

AF:

0.000261

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:

0.000473

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000420

AC:

614

AN:

1460506

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

295

AN XY:

726438

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000874

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:

0.000486

Gnomad4 OTH exome

AF:

0.000481

GnomAD4 genome

AF:

0.000722

AC:

110

AN:

152276

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000445

Hom.:

Bravo

AF:

0.00135

EpiCase

AF:

0.000600

EpiControl

AF:

0.000652

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZBTB7B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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