rs11974409

chr7-73575060-A-G

Variant summary

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

The NM_012453.4(TBL2):c.131-547T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 151,866 control chromosomes in the GnomAD database, including 2,090 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 0.16 (2090 hom., cov: 32)
• Consequence: TBL2 NM_012453.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBL2	NM_012453.4	c.131-547T>C		intron_variant		ENST00000305632.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBL2	ENST00000305632.11	c.131-547T>C		intron_variant		1	NM_012453.4	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24386 AN: 151748 Hom.: 2087 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0996

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.161 AC: 24404 AN: 151866 Hom.: 2090 Cov.: 32 AF XY: 0.158 AC XY: 11750 AN XY: 74214

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.0999

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.152

Alfa AF: 0.176 Hom.: 3155

Bravo AF: 0.156

Asia WGS AF: 0.110 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.68
Dann	Benign	0.30

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: rs11974409; hg19: chr7-72989390;