rs2496143

Positions:

• chr6-13311619-C-T

Variant summary

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

The NM_016495.6(TBC1D7):​c.520-3874G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,022 control chromosomes in the GnomAD database, including 21,551 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 0.51 (21551 hom., cov: 33)
• Consequence: TBC1D7 NM_016495.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873

Genes affected

TBC1D7 (HGNC:21066): (TBC1 domain family member 7) This gene encodes a member of the TBC-domain containing protein family. The encoded protein functions as a subunit of the tuberous sclerosis TSC1-TSC2 complex which plays a role in the regulation of cellular growth and differentiation. Mutations in this gene have been associated with autosomal recessive megalencephaly. Alternative splicing results in multiple transcript variants. Naturally occurring readthrough transcription occurs between this locus and downstream LOC100130357. [provided by RefSeq, Jan 2016]

TBC1D7-LOC100130357 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D7	NM_016495.6	c.520-3874G>A		intron_variant		ENST00000379300.8	NP_057579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D7	ENST00000379300.8	c.520-3874G>A		intron_variant		1	NM_016495.6	ENSP00000368602.3

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77811 AN: 151904 Hom.: 21505 Cov.: 33

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.513 AC: 77921 AN: 152022 Hom.: 21551 Cov.: 33 AF XY: 0.518 AC XY: 38447 AN XY: 74284

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.489

Alfa AF: 0.485 Hom.: 3650

Bravo AF: 0.529

Asia WGS AF: 0.678 AC: 2356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.012
DANN	Benign	0.20

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: rs2496143; hg19: chr6-13311851;