Variant 15-78012819-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_144572.2(TBC1D2B):c.2270+4G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,494,160 control chromosomes in the GnomAD database, including 186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0074 ( 11 hom., cov: 33)

Exomes 𝑓: 0.013 ( 175 hom. )

Consequence

TBC1D2B
NM_144572.2 splice_donor_region, intron

Scores

Splicing: ADA: 0.0001861

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.15

Variant links:

Genes affected

TBC1D2B (HGNC:29183): (TBC1 domain family member 2B) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 15-78012819-C-T is Benign according to our data. Variant chr15-78012819-C-T is described in ClinVar as [Benign]. Clinvar id is 1694761.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0074 (1128/152332) while in subpopulation NFE AF= 0.0132 (896/68034). AF 95% confidence interval is 0.0125. There are 11 homozygotes in gnomad4. There are 497 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D2B	NM_144572.2 linkuse as main transcript	c.2270+4G>A		splice_donor_region_variant, intron_variant		ENST00000300584.8	NP_653173.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
TBC1D2B	ENST00000300584.8 linkuse as main transcript	c.2270+4G>A	splice_donor_region_variant, intron_variant	5	NM_144572.2	ENSP00000300584	P1	Q9UPU7-1
TBC1D2B	ENST00000409931.7 linkuse as main transcript	c.2270+4G>A	splice_donor_region_variant, intron_variant	1		ENSP00000387165		Q9UPU7-2
TBC1D2B	ENST00000472786.1 linkuse as main transcript	n.1236+4G>A	splice_donor_region_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00742

AC:

1129

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00248

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00784

AC:

1349

AN:

172152

Hom.:

AF XY:

0.00774

AC XY:

701

AN XY:

90580

show subpopulations

Gnomad AFR exome

AF:

0.00196

Gnomad AMR exome

AF:

0.00793

Gnomad ASJ exome

AF:

0.00352

Gnomad EAS exome

AF:

0.0000649

Gnomad SAS exome

AF:

0.00200

Gnomad FIN exome

AF:

0.00373

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.00854

GnomAD4 exome

AF:

0.0135

AC:

18069

AN:

1341828

Hom.:

175

Cov.:

AF XY:

0.0130

AC XY:

8529

AN XY:

653808

show subpopulations

Gnomad4 AFR exome

AF:

0.00227

Gnomad4 AMR exome

AF:

0.00803

Gnomad4 ASJ exome

AF:

0.00347

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.00238

Gnomad4 FIN exome

AF:

0.00354

Gnomad4 NFE exome

AF:

0.0159

Gnomad4 OTH exome

AF:

0.0115

GnomAD4 genome

AF:

0.00740

AC:

1128

AN:

152332

Hom.:

Cov.:

AF XY:

0.00667

AC XY:

497

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00248

Gnomad4 AMR

AF:

0.00432

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.0132

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00952

Hom.:

Bravo

AF:

0.00765

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

TBC1D2B: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

4.1

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.030

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