rs729438

Positions:

• chr14-103626452-G-A

Variant summary

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

The ENST00000557172.5(KLC1):​c.-1-28112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,036 control chromosomes in the GnomAD database, including 5,762 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 0.26 (5762 hom., cov: 31)
• Consequence: KLC1 ENST00000557172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

Genes affected

KLC1 (HGNC:6387): (kinesin light chain 1) Conventional kinesin is a tetrameric molecule composed of two heavy chains and two light chains, and transports various cargos along microtubules toward their plus ends. The heavy chains provide the motor activity, while the light chains bind to various cargos. This gene encodes a member of the kinesin light chain family. It associates with kinesin heavy chain through an N-terminal domain, and six tetratricopeptide repeat (TPR) motifs are thought to be involved in binding of cargos such as vesicles, mitochondria, and the Golgi complex. Thus, kinesin light chains function as adapter molecules and not motors per se. Although previously named "kinesin 2", this gene is not a member of the kinesin-2 / kinesin heavy chain subfamily of kinesin motor proteins. Extensive alternative splicing produces isoforms with different C-termini that are proposed to bind to different cargos; however, the full-length nature and/or biological validity of most of these variants have not been determined. [provided by RefSeq, Jul 2008]

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 = 0.315 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLC1	ENST00000557172.5	c.-1-28112G>A		intron_variant		4		ENSP00000450786

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39804 AN: 151920 Hom.: 5748 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.262 AC: 39835 AN: 152036 Hom.: 5762 Cov.: 31 AF XY: 0.263 AC XY: 19534 AN XY: 74310

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.255

Alfa AF: 0.291 Hom.: 5320

Bravo AF: 0.251

Asia WGS AF: 0.249 AC: 868 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	0.38
DANN	Benign	0.89

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: rs729438; hg19: chr14-104092789;