rs202020

Variant names:

• chr6-13301685-C-G
• rs202020
• NM_001318809.2:c.*39+3377G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TBC1D7-LOC100130357	NM_001318809.2	c.*39+3377G>C		intron_variant	Intron 8 of 8		NP_001305738.1
TBC1D7-LOC100130357	NR_134872.2	n.610-6787G>C		intron_variant	Intron 5 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D7	ENST00000606214.5	c.*39+3377G>C		intron_variant	Intron 7 of 7	5		ENSP00000475727.1
TBC1D7	ENST00000421203.6	n.520-6787G>C		intron_variant	Intron 5 of 7	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

African (AFR) AF: 0.639 AC: 26531 AN: 41490

American (AMR) AF: 0.538 AC: 8229 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1677 AN: 3470

East Asian (EAS) AF: 0.670 AC: 3468 AN: 5174

South Asian (SAS) AF: 0.623 AC: 2996 AN: 4806

European-Finnish (FIN) AF: 0.418 AC: 4427 AN: 10588

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26328 AN: 67984

Other (OTH) AF: 0.471 AC: 992 AN: 2106

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
PhyloP100		-0.088
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs202020; hg19: chr6-13301917;