rs10519181

Positions:

• chr15-77996633-G-C
• chr15-77996633-G-T

Variant summary

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

The NM_144572.2(TBC1D2B):​c.*1527C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,238 control chromosomes in the GnomAD database, including 3,447 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 0.20 (3447 hom., cov: 34)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: TBC1D2B NM_144572.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844

Genes affected

TBC1D2B (HGNC:29183): (TBC1 domain family member 2B) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D2B	NM_144572.2	c.*1527C>G		3_prime_UTR_variant	13/13	ENST00000300584.8	NP_653173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D2B	ENST00000300584.8	c.*1527C>G		3_prime_UTR_variant	13/13	5	NM_144572.2	ENSP00000300584	P1
TBC1D2B	ENST00000409931.7	c.*1622C>G		3_prime_UTR_variant	13/13	1		ENSP00000387165
TBC1D2B	ENST00000465531.1	c.66+4986C>G		intron_variant		4		ENSP00000453114
TBC1D2B	ENST00000418039.2	n.2749C>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30275 AN: 152112 Hom.: 3444 Cov.: 34

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.250

GnomAD4 genome AF: 0.199 AC: 30286 AN: 152230 Hom.: 3447 Cov.: 34 AF XY: 0.203 AC XY: 15112 AN XY: 74430

Gnomad4 AFR AF: 0.0711

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.190

Alfa AF: 0.215 Hom.: 503

Bravo AF: 0.187

Asia WGS AF: 0.264 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs10519181; hg19: chr15-78288975;