14-103693804-T-C

Variant names:

• chr14-103693804-T-C
• rs2273175
• NM_001394837.1:c.1848+1379T>C

Variant summary

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

The NM_001394833.1(KLC1):​c.*186T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,401,218 control chromosomes in the GnomAD database, including 71,196 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 0.30 (7241 hom., cov: 33)
  • Exomes 𝑓: 0.32 (63955 hom.)
• Consequence: KLC1 NM_001394833.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLC1	NM_001394837.1	c.1848+1379T>C		intron_variant	Intron 15 of 16	ENST00000334553.11	NP_001381766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLC1	ENST00000334553.11	c.1848+1379T>C		intron_variant	Intron 15 of 16	5	NM_001394837.1	ENSP00000334523.6

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45311 AN: 152074 Hom.: 7227 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.317 AC: 395978 AN: 1249026 Hom.: 63955 Cov.: 32 AF XY: 0.313 AC XY: 189199 AN XY: 603710

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.419

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.297

GnomAD4 genome AF: 0.298 AC: 45348 AN: 152192 Hom.: 7241 Cov.: 33 AF XY: 0.299 AC XY: 22274 AN XY: 74392

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.277

Alfa AF: 0.297 Hom.: 6853

Bravo AF: 0.285

Asia WGS AF: 0.273 AC: 949 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	2.5
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2273175; hg19: chr14-104160141;