Variant 14-103562909-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.937

Variant links:

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]

KLC1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
	use as main transcript	n.103562909G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLC1	ENST00000557172.5 linkuse as main transcript	c.-2+925G>A		intron_variant		4		ENSP00000450786.1		G3V2P7

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44729

AN:

151870

Hom.:

6900

Cov.:

show subpopulations

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.:

AF XY:

0.335

AC XY:

193352

AN XY:

577804

show subpopulations

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.:

AF XY:

0.288

AC XY:

21374

AN XY:

74284

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over