rs17145738

Positions:

• chr7-73568544-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012453.4(TBL2):​c.*1963G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,128 control chromosomes in the GnomAD database, including 886 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (886 hom., cov: 32)
• Consequence: TBL2 NM_012453.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBL2	NM_012453.4	c.*1963G>A		3_prime_UTR_variant	7/7	ENST00000305632.11	NP_036585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBL2	ENST00000305632.11	c.*1963G>A		3_prime_UTR_variant	7/7	1	NM_012453.4	ENSP00000307260	P1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15941 AN: 152010 Hom.: 885 Cov.: 32

Gnomad AFR AF: 0.0872

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0991

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0932

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.105 AC: 15954 AN: 152128 Hom.: 886 Cov.: 32 AF XY: 0.105 AC XY: 7776 AN XY: 74364

Gnomad4 AFR AF: 0.0870

Gnomad4 AMR AF: 0.0772

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.0995

Gnomad4 SAS AF: 0.0883

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0970

Alfa AF: 0.113 Hom.: 1769

Bravo AF: 0.0990

Asia WGS AF: 0.101 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17145738; hg19: chr7-72982874;