15-73909588-T-G

Position:

• chr15-73909588-T-G

Variant summary

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

The XM_011521281.4(TBC1D21):​c.979-63T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,918 control chromosomes in the GnomAD database, including 14,183 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 0.41 (14183 hom., cov: 31)
• Consequence: TBC1D21 XM_011521281.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878

Genes affected

TBC1D21 (HGNC:28536): (TBC1 domain family member 21) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

LOXL1-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D21	XM_011521281.4	c.979-63T>G		intron_variant			XP_011519583.1
TBC1D21	XM_047432198.1	c.871-63T>G		intron_variant			XP_047288154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LOXL1-AS1	ENST00000565689.5	n.258-1040A>C		intron_variant		3
LOXL1-AS1	ENST00000568229.5	n.413-1040A>C		intron_variant		2
LOXL1-AS1	ENST00000685373.1	n.519-1040A>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61665 AN: 151800 Hom.: 14184 Cov.: 31

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.0545

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.406 AC: 61681 AN: 151918 Hom.: 14183 Cov.: 31 AF XY: 0.402 AC XY: 29871 AN XY: 74244

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.0546

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.392

Alfa AF: 0.412 Hom.: 2755

Bravo AF: 0.393

Asia WGS AF: 0.182 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12914677; hg19: chr15-74201929;