rs76294174

Positions:

• chr6-13293338-G-C

Variant summary

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

The NR_134872.2(TBC1D7-LOC100130357):​n.712+1458C>G variant causes a intron, non coding transcript 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 NR_134872.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

Genes affected

(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=-0.81).
• 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/exons	MANE	Protein	UniProt
TBC1D7-LOC100130357	NR_134872.2	n.712+1458C>G		intron_variant, non_coding_transcript_variant
TBC1D7-LOC100130357	NM_001318809.2	c.*39+11724C>G		intron_variant			NP_001305738.1
LOC100130357	NR_160971.1	n.318+1458C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000606150.5	n.318+1458C>G		intron_variant, non_coding_transcript_variant		2
TBC1D7	ENST00000606214.5	c.*39+11724C>G		intron_variant		5		ENSP00000475727	P1
TBC1D7	ENST00000421203.6	c.*82+1458C>G		intron_variant, NMD_transcript_variant		2		ENSP00000401438
	ENST00000612479.1	n.140+1458C>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.0134

Gnomad4 ASJ AF: 0.00807

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.0174

Gnomad4 FIN AF: 0.0647

Gnomad4 NFE AF: 0.00168

Gnomad4 OTH AF: 0.0132

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs76294174; hg19: chr6-13293570;