rs202020

Positions:

• chr6-13301685-C-G
• chr6-13301685-C-T

Variant summary

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

The NM_001318809.2(TBC1D7-LOC100130357):​c.*39+3377G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,110 control chromosomes in the GnomAD database, including 19,639 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 0.49 (19639 hom., cov: 32)
• Consequence: TBC1D7-LOC100130357 NM_001318809.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

Genes affected

TBC1D7-LOC100130357 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D7-LOC100130357	NM_001318809.2	c.*39+3377G>C		intron_variant			NP_001305738.1
TBC1D7-LOC100130357	NR_134872.2	n.610-6787G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D7	ENST00000606214.5	c.*39+3377G>C		intron_variant		5		ENSP00000475727.1
TBC1D7	ENST00000421203.6	n.520-6787G>C		intron_variant		2		ENSP00000401438.2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75017 AN: 151992 Hom.: 19605 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.494 AC: 75104 AN: 152110 Hom.: 19639 Cov.: 32 AF XY: 0.499 AC XY: 37104 AN XY: 74352

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.471

Alfa AF: 0.437 Hom.: 1930

Bravo AF: 0.507

Asia WGS AF: 0.671 AC: 2332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.5
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs202020; hg19: chr6-13301917;