14-103562909-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000557172.5(KLC1):c.-2+925G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,350,200 control chromosomes in the GnomAD database, including 76,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (6902 hom., cov: 34)
  • Exomes 𝑓: 0.34 (69257 hom.)
• Consequence: KLC1 ENST00000557172.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.937

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 14-103562909-G-A is Benign according to our data. Variant chr14-103562909-G-A is described in ClinVar as [Benign]. Clinvar id is 1270467.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLC1	ENST00000557172.5	c.-2+925G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44729 AN: 151870 Hom.: 6900 Cov.: 34

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.0795

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.336 AC: 402379 AN: 1198220 Hom.: 69257 Cov.: 30 AF XY: 0.335 AC XY: 193352 AN XY: 577804

Gnomad4 AFR exome AF: 0.259

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.346

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.316

GnomAD4 genome AF: 0.294 AC: 44732 AN: 151980 Hom.: 6902 Cov.: 34 AF XY: 0.288 AC XY: 21374 AN XY: 74284

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.0795

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.307

Alfa AF: 0.313 Hom.: 941

Bravo AF: 0.290

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

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	3.4
Dann	Benign	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2274269; hg19: chr14-104029246; COSMIC: COSV99914570;