rs2301818

Variant names:

• chr4-7004671-A-G
• rs2301818
• NM_020773.3:c.1271-173A>G

Variant summary

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

The NM_020773.3(TBC1D14):​c.1271-173A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,292 control chromosomes in the GnomAD database, including 1,019 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 0.10 (1019 hom., cov: 33)
• Consequence: TBC1D14 NM_020773.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 3 publications found

Genes affected

TBC1D14 (HGNC:29246): (TBC1 domain family member 14) Enables protein kinase binding activity. Involved in negative regulation of autophagy; recycling endosome to Golgi transport; and regulation of autophagosome assembly. Located in several cellular components, including Golgi apparatus; autophagosome; and recycling endosome. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D14	NM_020773.3	c.1271-173A>G		intron_variant	Intron 7 of 13	ENST00000409757.9	NP_065824.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D14	ENST00000409757.9	c.1271-173A>G		intron_variant	Intron 7 of 13	1	NM_020773.3	ENSP00000386921.4

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15394 AN: 152174 Hom.: 1017 Cov.: 33

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0244

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.101 AC: 15396 AN: 152292 Hom.: 1019 Cov.: 33 AF XY: 0.102 AC XY: 7623 AN XY: 74468

African (AFR) AF: 0.0236 AC: 983 AN: 41570

American (AMR) AF: 0.118 AC: 1809 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 602 AN: 3470

East Asian (EAS) AF: 0.0247 AC: 128 AN: 5192

South Asian (SAS) AF: 0.188 AC: 909 AN: 4824

European-Finnish (FIN) AF: 0.113 AC: 1197 AN: 10602

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9228 AN: 68032

Other (OTH) AF: 0.124 AC: 262 AN: 2116

Alfa AF: 0.132 Hom.: 765

Bravo AF: 0.0936

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.072
DANN	Benign	0.76
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2301818; hg19: chr4-7006398;