rs480122

Positions:

• chr6-13316852-C-A
• chr6-13316852-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016495.6(TBC1D7):​c.382-144G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 962,006 control chromosomes in the GnomAD database, including 24,615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3514 hom., cov: 32)
  • Exomes 𝑓: 0.21 (21101 hom.)
• Consequence: TBC1D7 NM_016495.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.108

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-13316852-C-A is Benign according to our data. Variant chr6-13316852-C-A is described in ClinVar as [Benign]. Clinvar id is 1228650.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D7	NM_016495.6	c.382-144G>T		intron_variant		ENST00000379300.8	NP_057579.1
TBC1D7-LOC100130357	NR_134872.2	n.472-144G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D7	ENST00000379300.8	c.382-144G>T		intron_variant		1	NM_016495.6	ENSP00000368602	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31260 AN: 152046 Hom.: 3519 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.213 AC: 172371 AN: 809840 Hom.: 21101 AF XY: 0.219 AC XY: 91062 AN XY: 415870

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.392

Gnomad4 SAS exome AF: 0.365

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.205 AC: 31263 AN: 152166 Hom.: 3514 Cov.: 32 AF XY: 0.208 AC XY: 15505 AN XY: 74402

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.211

Alfa AF: 0.209 Hom.: 4590

Bravo AF: 0.205

Asia WGS AF: 0.387 AC: 1344 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.68

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: rs480122; hg19: chr6-13317084; COSMIC: COSV58245426; COSMIC: COSV58245426;