14-103671306-A-G

Variant names:

• chr14-103671306-A-G
• rs8007903
• NM_001394837.1:c.987+1023A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.91).
• 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 rank	MANE	Protein	UniProt
KLC1	NM_001394837.1	c.987+1023A>G		intron_variant	Intron 7 of 16	ENST00000334553.11	NP_001381766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLC1	ENST00000334553.11	c.987+1023A>G		intron_variant	Intron 7 of 16	5	NM_001394837.1	ENSP00000334523.6
ENSG00000256500	ENST00000472726.3	c.1464+1023A>G		intron_variant	Intron 10 of 17	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

African (AFR) AF: 0.344 AC: 14231 AN: 41394

American (AMR) AF: 0.322 AC: 4919 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 884 AN: 3466

East Asian (EAS) AF: 0.534 AC: 2765 AN: 5180

South Asian (SAS) AF: 0.411 AC: 1984 AN: 4826

European-Finnish (FIN) AF: 0.243 AC: 2571 AN: 10586

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13626 AN: 67994

Other (OTH) AF: 0.283 AC: 599 AN: 2116

Alfa AF: 0.239 Hom.: 3496

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
PhyloP100		-0.14
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: rs8007903; hg19: chr14-104137643;