Variant chr7-73570975-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_012453.4(TBL2):c.879-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000656 in 1,592,812 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 2 hom. )

Consequence

TBL2
NM_012453.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.001760

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.51

Variant links:

Genes affected

TBL2 (HGNC:11586): (transducin beta like 2) This gene encodes a member of the beta-transducin protein family. Most proteins of the beta-transducin family are involved in regulatory functions. This protein is possibly involved in some intracellular signaling pathway. This gene is deleted in Williams-Beuren syndrome, a developmental disorder caused by deletion of multiple genes at 7q11.23. [provided by RefSeq, Jul 2008]

TBL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 7-73570975-G-A is Benign according to our data. Variant chr7-73570975-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3025915.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBL2	NM_012453.4 linkuse as main transcript	c.879-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000305632.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBL2	ENST00000305632.11 linkuse as main transcript	c.879-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_012453.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000676

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000210

AC:

AN:

232904

Hom.:

AF XY:

0.000223

AC XY:

AN XY:

125570

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.0000305

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:

0.000428

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.000689

AC:

992

AN:

1440438

Hom.:

Cov.:

AF XY:

0.000641

AC XY:

458

AN XY:

714022

show subpopulations

Gnomad4 AFR exome

AF:

0.000213

Gnomad4 AMR exome

AF:

0.0000233

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:

0.000820

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

AF:

0.000348

AC:

AN:

152374

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000661

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000450

Hom.:

Bravo

AF:

0.000363

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

TBL2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.7

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0018

dbscSNV1_RF

Benign

0.052

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