rs729438

Variant names:

• chr14-103626452-G-A
• rs729438
• ENST00000472726.3:c.477-28112G>A

Variant summary

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

The ENST00000472726.3(ENSG00000256500):​c.477-28112G>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: ENSG00000256500 ENST00000472726.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 16 publications found

Genes affected

ENSG00000256500 (HGNC:):

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000256500	ENST00000472726.3	c.477-28112G>A		intron_variant	Intron 4 of 17	2		ENSP00000439065.2
KLC1	ENST00000557172.5	c.-1-28112G>A		intron_variant	Intron 1 of 2	4		ENSP00000450786.1

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

African (AFR) AF: 0.152 AC: 6325 AN: 41484

American (AMR) AF: 0.280 AC: 4279 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 898 AN: 3470

East Asian (EAS) AF: 0.328 AC: 1690 AN: 5154

South Asian (SAS) AF: 0.185 AC: 889 AN: 4812

European-Finnish (FIN) AF: 0.382 AC: 4041 AN: 10568

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.306 AC: 20819 AN: 67968

Other (OTH) AF: 0.255 AC: 537 AN: 2108

Alfa AF: 0.291 Hom.: 7489

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
PhyloP100		-1.3

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: rs729438; hg19: chr14-104092789;