chr14-103694944-G-A

Variant names:

• chr14-103694944-G-A
• rs1606
• NM_001394837.1:c.1848+2519G>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+2519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 985,234 control chromosomes in the GnomAD database, including 49,001 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 0.28 (6698 hom., cov: 32)
  • Exomes 𝑓: 0.32 (42303 hom.)
• Consequence: KLC1 NM_001394837.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 8 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]

ENSG00000269940 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 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+2519G>A		intron	N/A	NP_001381766.1
	KLC1	NM_001394833.1		c.*1326G>A		3_prime_UTR	Exon 16 of 16	NP_001381762.1
	KLC1	NM_001394835.1		c.*1326G>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+2519G>A		intron	N/A	ENSP00000334523.6
	KLC1	ENST00000348520.10	TSL:1	c.1651-5711G>A		intron	N/A	ENSP00000341154.6
	ENSG00000269940	ENST00000602669.1	TSL:6	n.385G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42508 AN: 152014 Hom.: 6685 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.318 AC: 264654 AN: 833102 Hom.: 42303 Cov.: 31 AF XY: 0.316 AC XY: 121543 AN XY: 384708

African (AFR) AF: 0.134 AC: 2123 AN: 15786

American (AMR) AF: 0.319 AC: 314 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 1033 AN: 5150

East Asian (EAS) AF: 0.350 AC: 1271 AN: 3630

South Asian (SAS) AF: 0.205 AC: 3379 AN: 16460

European-Finnish (FIN) AF: 0.383 AC: 108 AN: 282

Middle Eastern (MID) AF: 0.190 AC: 307 AN: 1620

European-Non Finnish (NFE) AF: 0.326 AC: 248136 AN: 761890

Other (OTH) AF: 0.292 AC: 7983 AN: 27300

GnomAD4 genome AF: 0.280 AC: 42537 AN: 152132 Hom.: 6698 Cov.: 32 AF XY: 0.281 AC XY: 20871 AN XY: 74352

African (AFR) AF: 0.157 AC: 6532 AN: 41510

American (AMR) AF: 0.288 AC: 4406 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3466

East Asian (EAS) AF: 0.348 AC: 1804 AN: 5178

South Asian (SAS) AF: 0.201 AC: 973 AN: 4830

European-Finnish (FIN) AF: 0.433 AC: 4563 AN: 10544

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22633 AN: 67998

Other (OTH) AF: 0.263 AC: 554 AN: 2110

Alfa AF: 0.304 Hom.: 992

Bravo AF: 0.264

Asia WGS AF: 0.258 AC: 897 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.54
DANN	Benign	0.76
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs1606; hg19: chr14-104161281;