chr3-18269920-G-A

Variant names:

• chr3-18269920-G-A
• rs7641175
• ENST00000414318.2:n.211+174687C>T

Variant summary

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

The ENST00000414318.2(TBC1D5):​n.211+174687C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 151,918 control chromosomes in the GnomAD database, including 49,924 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 0.81 (49924 hom., cov: 30)
• Consequence: TBC1D5 ENST00000414318.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453
• Publications: 20 publications found

Genes affected

TBC1D5 (HGNC:19166): (TBC1 domain family member 5) Enables AP-2 adaptor complex binding activity and retromer complex binding activity. Involved in several processes, including macroautophagy; positive regulation of receptor internalization; and retrograde transport, endosome to Golgi. Located in Golgi apparatus; autophagosome; and endosome membrane. Part of retromer complex. Colocalizes with AP-2 adaptor complex and Atg1/ULK1 kinase complex. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D5	ENST00000414318.2	n.211+174687C>T		intron_variant	Intron 1 of 8	5

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122709 AN: 151800 Hom.: 49886 Cov.: 30

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.808 AC: 122804 AN: 151918 Hom.: 49924 Cov.: 30 AF XY: 0.810 AC XY: 60095 AN XY: 74234

African (AFR) AF: 0.866 AC: 35930 AN: 41476

American (AMR) AF: 0.832 AC: 12698 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2413 AN: 3470

East Asian (EAS) AF: 0.939 AC: 4854 AN: 5172

South Asian (SAS) AF: 0.790 AC: 3805 AN: 4816

European-Finnish (FIN) AF: 0.792 AC: 8352 AN: 10542

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52113 AN: 67872

Other (OTH) AF: 0.804 AC: 1694 AN: 2106

Alfa AF: 0.784 Hom.: 172576

Bravo AF: 0.817

Asia WGS AF: 0.866 AC: 3012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.44
PhyloP100		0.45

Splicing

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

Other links and lift over

dbSNP: rs7641175; hg19: chr3-18311412;