rs1606

Positions:

• chr14-103694944-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+2519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 985,234 control chromosomes in the GnomAD database, including 49,001 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 0.28 (6698 hom., cov: 32)
  • Exomes 𝑓: 0.32 (42303 hom.)
• Consequence: KLC1 NM_001394837.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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]

(HGNC:):

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 = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLC1	NM_001394837.1	c.1848+2519G>A		intron_variant		ENST00000334553.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLC1	ENST00000334553.11	c.1848+2519G>A		intron_variant		5	NM_001394837.1
	ENST00000602669.1	n.385G>A		non_coding_transcript_exon_variant	1/1
	ENST00000602722.1	n.107C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42508 AN: 152014 Hom.: 6685 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.318 AC: 264654 AN: 833102 Hom.: 42303 Cov.: 31 AF XY: 0.316 AC XY: 121543 AN XY: 384708

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.319

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.350

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.383

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.292

GnomAD4 genome AF: 0.280 AC: 42537 AN: 152132 Hom.: 6698 Cov.: 32 AF XY: 0.281 AC XY: 20871 AN XY: 74352

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.263

Alfa AF: 0.311 Hom.: 983

Bravo AF: 0.264

Asia WGS AF: 0.258 AC: 897 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.54
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1606; hg19: chr14-104161281;