chr14-103671306-A-G

Position:

• chr14-103671306-A-G

Variant summary

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

The NM_001394837.1(KLC1):​c.987+1023A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,030 control chromosomes in the GnomAD database, including 6,361 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 0.27 (6361 hom., cov: 32)
• Consequence: KLC1 NM_001394837.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139

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]

ENSG00000256500 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLC1	NM_001394837.1	c.987+1023A>G		intron_variant		ENST00000334553.11	NP_001381766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLC1	ENST00000334553.11	c.987+1023A>G		intron_variant		5	NM_001394837.1	ENSP00000334523.6
ENSG00000256500	ENST00000472726.3	c.1464+1023A>G		intron_variant		2		ENSP00000439065.2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41753 AN: 151918 Hom.: 6344 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.278

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.275 AC: 41791 AN: 152030 Hom.: 6361 Cov.: 32 AF XY: 0.283 AC XY: 21047 AN XY: 74330

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.283

Alfa AF: 0.229 Hom.: 2157

Bravo AF: 0.284

Asia WGS AF: 0.486 AC: 1689 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	1.9
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8007903; hg19: chr14-104137643;