14-103562851-C-CCCG

Position:

• chr14-103562851-C-CCCG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000557172.5(KLC1):​c.-2+867_-2+868insCCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,146,862 control chromosomes in the GnomAD database, including 40,974 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4970 hom., cov: 26)
  • Exomes 𝑓: 0.26 (36004 hom.)
• Consequence: KLC1 ENST00000557172.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.480

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 -10 ACMG points.

• BP6: Variant 14-103562851-C-CCCG is Benign according to our data. Variant chr14-103562851-C-CCCG is described in ClinVar as [Benign]. Clinvar id is 1244059.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.103562851_103562852insCCG		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLC1	ENST00000557172.5	c.-2+867_-2+868insCCG		intron_variant		4		ENSP00000450786.1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 36875 AN: 151206 Hom.: 4954 Cov.: 26

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.262 AC: 261079 AN: 995548 Hom.: 36004 Cov.: 15 AF XY: 0.260 AC XY: 124072 AN XY: 477390

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.288

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.288

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.244 AC: 36899 AN: 151314 Hom.: 4970 Cov.: 26 AF XY: 0.244 AC XY: 18037 AN XY: 73958

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.241

Alfa AF: 0.262 Hom.: 568

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28362583; hg19: chr14-104029188;