14-103686015-C-G

Variant names:

• chr14-103686015-C-G
• rs8702
• ENST00000389744.8:c.*396C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000389744.8(KLC1):​c.*396C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,072,006 control chromosomes in the GnomAD database, including 244,784 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 0.61 (29003 hom., cov: 33)
  • Exomes 𝑓: 0.68 (215781 hom.)
• Consequence: KLC1 ENST00000389744.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLC1	NM_001394837.1	c.1651-1066C>G		intron_variant	Intron 13 of 16	ENST00000334553.11	NP_001381766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLC1	ENST00000334553.11	c.1651-1066C>G		intron_variant	Intron 13 of 16	5	NM_001394837.1	ENSP00000334523.6
ENSG00000256500	ENST00000472726.3	c.*396C>G		downstream_gene_variant		2		ENSP00000439065.2

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92077 AN: 151980 Hom.: 28979 Cov.: 33

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.682 AC: 627489 AN: 919908 Hom.: 215781 Cov.: 40 AF XY: 0.679 AC XY: 292875 AN XY: 431402

African (AFR) AF: 0.459 AC: 8348 AN: 18200

American (AMR) AF: 0.558 AC: 2763 AN: 4956

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 4417 AN: 7180

East Asian (EAS) AF: 0.440 AC: 3222 AN: 7330

South Asian (SAS) AF: 0.468 AC: 14588 AN: 31194

European-Finnish (FIN) AF: 0.726 AC: 2704 AN: 3726

Middle Eastern (MID) AF: 0.582 AC: 1132 AN: 1944

European-Non Finnish (NFE) AF: 0.701 AC: 570176 AN: 813822

Other (OTH) AF: 0.638 AC: 20139 AN: 31556

GnomAD4 genome AF: 0.606 AC: 92138 AN: 152098 Hom.: 29003 Cov.: 33 AF XY: 0.601 AC XY: 44661 AN XY: 74354

African (AFR) AF: 0.459 AC: 19015 AN: 41464

American (AMR) AF: 0.559 AC: 8538 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2187 AN: 3472

East Asian (EAS) AF: 0.447 AC: 2315 AN: 5182

South Asian (SAS) AF: 0.445 AC: 2148 AN: 4824

European-Finnish (FIN) AF: 0.722 AC: 7632 AN: 10574

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48211 AN: 67978

Other (OTH) AF: 0.596 AC: 1261 AN: 2116

Alfa AF: 0.581 Hom.: 1875

Bravo AF: 0.588

Asia WGS AF: 0.409 AC: 1426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.53
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8702; hg19: chr14-104152352;