chr14-103695926-G-A

Variant names:

• chr14-103695926-G-A
• rs861544
• NM_001394837.1:c.1848+3501G>A

Variant summary

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

The NM_001394837.1(KLC1):​c.1848+3501G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 985,110 control chromosomes in the GnomAD database, including 219,781 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 0.60 (28616 hom., cov: 32)
  • Exomes 𝑓: 0.68 (191165 hom.)
• Consequence: KLC1 NM_001394837.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682
• Publications: 14 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394837.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLC1	NM_001394837.1	MANE Select	c.1848+3501G>A		intron	N/A	NP_001381766.1
	KLC1	NM_001394833.1		c.*2308G>A		3_prime_UTR	Exon 16 of 16	NP_001381762.1
	KLC1	NM_001394835.1		c.*2308G>A		3_prime_UTR	Exon 16 of 16	NP_001381764.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLC1	ENST00000334553.11	TSL:5 MANE Select	c.1848+3501G>A		intron	N/A	ENSP00000334523.6
	KLC1	ENST00000348520.10	TSL:1	c.1651-4729G>A		intron	N/A	ENSP00000341154.6
	KLC1	ENST00000555836.5	TSL:5	c.1821+3501G>A		intron	N/A	ENSP00000452481.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91668 AN: 151938 Hom.: 28592 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.601

GnomAD4 exome AF: 0.676 AC: 563252 AN: 833054 Hom.: 191165 Cov.: 37 AF XY: 0.675 AC XY: 259834 AN XY: 384698

African (AFR) AF: 0.468 AC: 7385 AN: 15770

American (AMR) AF: 0.569 AC: 560 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 3186 AN: 5150

East Asian (EAS) AF: 0.454 AC: 1648 AN: 3630

South Asian (SAS) AF: 0.461 AC: 7583 AN: 16458

European-Finnish (FIN) AF: 0.719 AC: 197 AN: 274

Middle Eastern (MID) AF: 0.575 AC: 932 AN: 1620

European-Non Finnish (NFE) AF: 0.689 AC: 524692 AN: 761872

Other (OTH) AF: 0.625 AC: 17069 AN: 27296

GnomAD4 genome AF: 0.603 AC: 91732 AN: 152056 Hom.: 28616 Cov.: 32 AF XY: 0.598 AC XY: 44479 AN XY: 74340

African (AFR) AF: 0.468 AC: 19371 AN: 41416

American (AMR) AF: 0.559 AC: 8546 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2208 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2331 AN: 5176

South Asian (SAS) AF: 0.437 AC: 2102 AN: 4812

European-Finnish (FIN) AF: 0.719 AC: 7621 AN: 10596

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47454 AN: 67974

Other (OTH) AF: 0.598 AC: 1265 AN: 2116

Alfa AF: 0.631 Hom.: 18769

Bravo AF: 0.586

Asia WGS AF: 0.407 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.72
DANN	Benign	0.49
PhyloP100		-0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs861544; hg19: chr14-104162263; COSMIC: COSV55808387; COSMIC: COSV55808387;