rs2496143

Variant names:

• chr6-13311619-C-T
• rs2496143
• NM_016495.6:c.520-3874G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• macrocephaly/megalencephaly syndrome, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

TBC1D7-LOC100130357 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016495.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D7	NM_016495.6	MANE Select	c.520-3874G>A		intron	N/A	NP_057579.1
	TBC1D7	NM_001143964.4		c.520-3874G>A		intron	N/A	NP_001137436.1
	TBC1D7	NM_001143965.4		c.520-3874G>A		intron	N/A	NP_001137437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D7	ENST00000379300.8	TSL:1 MANE Select	c.520-3874G>A		intron	N/A	ENSP00000368602.3
	TBC1D7	ENST00000356436.8	TSL:1	c.520-3874G>A		intron	N/A	ENSP00000348813.4
	TBC1D7	ENST00000379307.6	TSL:1	c.439-3874G>A		intron	N/A	ENSP00000368609.2

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

African (AFR) AF: 0.708 AC: 29349 AN: 41470

American (AMR) AF: 0.546 AC: 8342 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1675 AN: 3472

East Asian (EAS) AF: 0.670 AC: 3466 AN: 5174

South Asian (SAS) AF: 0.617 AC: 2978 AN: 4826

European-Finnish (FIN) AF: 0.418 AC: 4398 AN: 10532

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26213 AN: 67962

Other (OTH) AF: 0.489 AC: 1033 AN: 2114

Alfa AF: 0.490 Hom.: 3835

Bravo AF: 0.529

Asia WGS AF: 0.678 AC: 2356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.012
DANN	Benign	0.20
PhyloP100		-0.87
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: rs2496143; hg19: chr6-13311851;