rs11974409

Variant names:

• chr7-73575060-A-G
• rs11974409
• NM_012453.4:c.131-547T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 37 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TBL2	NM_012453.4	c.131-547T>C		intron_variant	Intron 1 of 6	ENST00000305632.11	NP_036585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBL2	ENST00000305632.11	c.131-547T>C		intron_variant	Intron 1 of 6	1	NM_012453.4	ENSP00000307260.4

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

African (AFR) AF: 0.144 AC: 5970 AN: 41406

American (AMR) AF: 0.121 AC: 1845 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 568 AN: 3462

East Asian (EAS) AF: 0.100 AC: 518 AN: 5178

South Asian (SAS) AF: 0.0999 AC: 482 AN: 4824

European-Finnish (FIN) AF: 0.160 AC: 1679 AN: 10498

Middle Eastern (MID) AF: 0.145 AC: 42 AN: 290

European-Non Finnish (NFE) AF: 0.189 AC: 12843 AN: 67930

Other (OTH) AF: 0.152 AC: 319 AN: 2102

Alfa AF: 0.172 Hom.: 4091

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11974409; hg19: chr7-72989390;