rs12914489

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

Genes affected

TBC1D21 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TBC1D21	XM_011521281.4	c.978+7083G>A		intron_variant			XP_011519583.1
TBC1D21	XM_011521282.3	c.979-5400G>A		intron_variant			XP_011519584.1
TBC1D21	XM_011521283.3	c.978+7083G>A		intron_variant			XP_011519585.1
TBC1D21	XM_047432198.1	c.870+7083G>A		intron_variant			XP_047288154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	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

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.0464

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.0172

Gnomad4 SAS AF: 0.0627

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0772 Hom.: 207

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12914489; hg19: chr15-74187937;