rs55736920

Positions:

• chr15-73902673-C-T

Variant summary

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

The XM_011521281.4(TBC1D21):​c.979-6978C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,236 control chromosomes in the GnomAD database, including 1,443 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 0.12 (1443 hom., cov: 32)
• Consequence: TBC1D21 XM_011521281.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D21	XM_011521281.4	c.979-6978C>T		intron_variant			XP_011519583.1
TBC1D21	XM_011521283.3	c.979-4569C>T		intron_variant			XP_011519585.1
TBC1D21	XM_047432198.1	c.871-6978C>T		intron_variant			XP_047288154.1
		n.73902673C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18444 AN: 152118 Hom.: 1444 Cov.: 32

Gnomad AFR AF: 0.0605

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.0729

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.121 AC: 18441 AN: 152236 Hom.: 1443 Cov.: 32 AF XY: 0.118 AC XY: 8806 AN XY: 74430

Gnomad4 AFR AF: 0.0605

Gnomad4 AMR AF: 0.0809

Gnomad4 ASJ AF: 0.0991

Gnomad4 EAS AF: 0.0174

Gnomad4 SAS AF: 0.0726

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.102

Alfa AF: 0.156 Hom.: 256

Bravo AF: 0.110

Asia WGS AF: 0.0540 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs55736920; hg19: chr15-74195014;