XM_011521281.4:c.978+7083G>A

Variant names:

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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D21	XM_011521281.4	c.978+7083G>A		intron_variant	Intron 10 of 10		XP_011519583.1
TBC1D21	XM_011521282.3	c.979-5400G>A		intron_variant	Intron 10 of 10		XP_011519584.1
TBC1D21	XM_011521283.3	c.978+7083G>A		intron_variant	Intron 10 of 10		XP_011519585.1
TBC1D21	XM_047432198.1	c.870+7083G>A		intron_variant	Intron 9 of 9		XP_047288154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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 v4.3

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;