rs861544

chr14-103695926-G-A

Variant summary

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

The NM_001394837.1(KLC1):c.1848+3501G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 985,110 control chromosomes in the GnomAD database, including 219,781 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 0.60 (28616 hom., cov: 32)
  • Exomes 𝑓: 0.68 (191165 hom.)
• Consequence: KLC1 NM_001394837.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLC1	NM_001394837.1	c.1848+3501G>A		intron_variant		ENST00000334553.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLC1	ENST00000334553.11	c.1848+3501G>A		intron_variant		5	NM_001394837.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91668 AN: 151938 Hom.: 28592 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.601

GnomAD4 exome AF: 0.676 AC: 563252 AN: 833054 Hom.: 191165 Cov.: 37 AF XY: 0.675 AC XY: 259834 AN XY: 384698

Gnomad4 AFR exome AF: 0.468

Gnomad4 AMR exome AF: 0.569

Gnomad4 ASJ exome AF: 0.619

Gnomad4 EAS exome AF: 0.454

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.719

Gnomad4 NFE exome AF: 0.689

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.603 AC: 91732 AN: 152056 Hom.: 28616 Cov.: 32 AF XY: 0.598 AC XY: 44479 AN XY: 74340

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.598

Alfa AF: 0.657 Hom.: 15400

Bravo AF: 0.586

Asia WGS AF: 0.407 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.72
Dann	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs861544; hg19: chr14-104162263; COSMIC: COSV55808387; COSMIC: COSV55808387;