rs76294174

Variant names:

• chr6-13293338-G-C
• rs76294174
• NM_001318809.2:c.*39+11724C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-13293338-G-C
• chr6-13293338-G-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+11724C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 152,278 control chromosomes in the GnomAD database, including 87 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 0.013 (87 hom., cov: 33)
• Consequence: TBC1D7-LOC100130357 NM_001318809.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D7-LOC100130357	NM_001318809.2	c.*39+11724C>G		intron_variant	Intron 8 of 8		NP_001305738.1
TBC1D7-LOC100130357	NR_134872.2	n.712+1458C>G		intron_variant	Intron 6 of 7
LOC100130357	NR_160971.1	n.318+1458C>G		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D7	ENST00000606214.5	c.*39+11724C>G		intron_variant	Intron 7 of 7	5		ENSP00000475727.1
TBC1D7	ENST00000421203.6	n.*82+1458C>G		intron_variant	Intron 6 of 7	2		ENSP00000401438.2
ENSG00000215022	ENST00000606150.5	n.318+1458C>G		intron_variant	Intron 3 of 4	2
ENSG00000215022	ENST00000612479.1	n.140+1458C>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1967 AN: 152160 Hom.: 87 Cov.: 33

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.0647

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00168

Gnomad OTH AF: 0.0134

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

GnomAD4 genome AF: 0.0129 AC: 1970 AN: 152278 Hom.: 87 Cov.: 33 AF XY: 0.0167 AC XY: 1244 AN XY: 74456

African (AFR) AF: 0.000722 AC: 30 AN: 41564

American (AMR) AF: 0.0134 AC: 205 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 28 AN: 3470

East Asian (EAS) AF: 0.154 AC: 795 AN: 5176

South Asian (SAS) AF: 0.0174 AC: 84 AN: 4828

European-Finnish (FIN) AF: 0.0647 AC: 686 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00168 AC: 114 AN: 68008

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.00619 Hom.: 0

Bravo AF: 0.0111

Asia WGS AF: 0.0860 AC: 300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.68
DANN	Benign	0.82
PhyloP100		-0.33
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: rs76294174; hg19: chr6-13293570;