rs4689558

Positions:

• chr4-6918739-G-A
• chr4-6918739-G-C

Variant summary

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

The NM_020773.3(TBC1D14):​c.-17-4634G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,954 control chromosomes in the GnomAD database, including 16,220 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 0.46 (16220 hom., cov: 33)
• Consequence: TBC1D14 NM_020773.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373

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

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 = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D14	NM_020773.3	c.-17-4634G>A		intron_variant		ENST00000409757.9	NP_065824.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D14	ENST00000409757.9	c.-17-4634G>A		intron_variant		1	NM_020773.3	ENSP00000386921
TBC1D14	ENST00000427736.1	c.-17-4634G>A		intron_variant		2		ENSP00000411760
TBC1D14	ENST00000444368.1	c.-17-4634G>A		intron_variant		3		ENSP00000414951
TBC1D14	ENST00000448507.5	c.-17-4634G>A		intron_variant		5		ENSP00000404041

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69156 AN: 151836 Hom.: 16217 Cov.: 33

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.455 AC: 69171 AN: 151954 Hom.: 16220 Cov.: 33 AF XY: 0.459 AC XY: 34098 AN XY: 74256

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.469

Alfa AF: 0.472 Hom.: 9137

Bravo AF: 0.450

Asia WGS AF: 0.577 AC: 2009 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	1.3
DANN	Benign	0.22

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: rs4689558; hg19: chr4-6920466; COSMIC: COSV68987507;