rs12914489

Variant names:

• chr15-73895596-G-A
• rs12914489
• XM_011521281.4:c.978+7083G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-73895596-G-A
• chr15-73895596-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011521281.4(TBC1D21):​c.978+7083G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0804 in 152,240 control chromosomes in the GnomAD database, including 651 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 0.080 (651 hom., cov: 32)
• Consequence: TBC1D21 XM_011521281.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.854
• Publications: 11 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.0804 AC: 12235 AN: 152122 Hom.: 651 Cov.: 32

Gnomad AFR AF: 0.0503

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.0173

Gnomad SAS AF: 0.0633

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0583

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

GnomAD4 genome AF: 0.0804 AC: 12237 AN: 152240 Hom.: 651 Cov.: 32 AF XY: 0.0795 AC XY: 5917 AN XY: 74428

African (AFR) AF: 0.0503 AC: 2089 AN: 41544

American (AMR) AF: 0.0464 AC: 710 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3470

East Asian (EAS) AF: 0.0172 AC: 89 AN: 5184

South Asian (SAS) AF: 0.0627 AC: 303 AN: 4832

European-Finnish (FIN) AF: 0.135 AC: 1432 AN: 10594

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7310 AN: 68006

Other (OTH) AF: 0.0582 AC: 123 AN: 2114

Alfa AF: 0.0803 Hom.: 406

Bravo AF: 0.0703

Asia WGS AF: 0.0450 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.61
PhyloP100		0.85

Splicing

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

Other links and lift over

dbSNP: rs12914489; hg19: chr15-74187937;