rs480122

Variant names:

• chr6-13316852-C-A
• rs480122
• NM_016495.6:c.382-144G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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: Genomics England PanelApp, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

TBC1D7-LOC100130357 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D7	NM_016495.6	MANE Select	c.382-144G>T		intron	N/A	NP_057579.1	Q9P0N9-1
	TBC1D7	NM_001143964.4		c.382-144G>T		intron	N/A	NP_001137436.1	Q9P0N9-1
	TBC1D7	NM_001143965.4		c.382-144G>T		intron	N/A	NP_001137437.1	Q9P0N9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D7	ENST00000379300.8	TSL:1 MANE Select	c.382-144G>T		intron	N/A	ENSP00000368602.3	Q9P0N9-1
	TBC1D7	ENST00000356436.8	TSL:1	c.382-144G>T		intron	N/A	ENSP00000348813.4	Q9P0N9-1
	TBC1D7	ENST00000379307.6	TSL:1	c.301-144G>T		intron	N/A	ENSP00000368609.2	Q9P0N9-2

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

African (AFR) AF: 0.158 AC: 3035 AN: 19196

American (AMR) AF: 0.261 AC: 6267 AN: 24052

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 3952 AN: 16652

East Asian (EAS) AF: 0.392 AC: 13523 AN: 34522

South Asian (SAS) AF: 0.365 AC: 20128 AN: 55178

European-Finnish (FIN) AF: 0.151 AC: 4911 AN: 32614

Middle Eastern (MID) AF: 0.254 AC: 718 AN: 2822

European-Non Finnish (NFE) AF: 0.190 AC: 111631 AN: 586776

Other (OTH) AF: 0.216 AC: 8206 AN: 38028

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

African (AFR) AF: 0.159 AC: 6591 AN: 41518

American (AMR) AF: 0.245 AC: 3746 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 813 AN: 3466

East Asian (EAS) AF: 0.415 AC: 2144 AN: 5168

South Asian (SAS) AF: 0.383 AC: 1844 AN: 4818

European-Finnish (FIN) AF: 0.157 AC: 1668 AN: 10596

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13780 AN: 67994

Other (OTH) AF: 0.211 AC: 445 AN: 2114

Alfa AF: 0.207 Hom.: 6934

Bravo AF: 0.205

Asia WGS AF: 0.387 AC: 1344 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		-0.11
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: rs480122; hg19: chr6-13317084; COSMIC: COSV58245426; COSMIC: COSV58245426;