Genetic Variant NM_001394837.1:c.1848+1379T>C (chr14-103693804-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001394837.1(KLC1):c.1848+1379T>C variant causes a intron 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_001394837.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.328

Publications

12 publications found

Variant links:

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]

KLC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	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 link	c.1848+1379T>C		intron_variant	Intron 15 of 16	5	NM_001394837.1	ENSP00000334523.6		Q07866-9

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45311

AN:

152074

Hom.:

7227

Cov.:

show subpopulations

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.:

AF XY:

0.313

AC XY:

189199

AN XY:

603710

show subpopulations

African (AFR)

AF:

0.213

AC:

5728

AN:

26938

American (AMR)

AF:

0.317

AC:

5310

AN:

16732

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

3789

AN:

18144

East Asian (EAS)

AF:

0.344

AC:

10956

AN:

31894

South Asian (SAS)

AF:

0.208

AC:

12167

AN:

58534

European-Finnish (FIN)

AF:

0.419

AC:

12021

AN:

28664

Middle Eastern (MID)

AF:

0.204

AC:

704

AN:

3458

European-Non Finnish (NFE)

AF:

0.326

AC:

329982

AN:

1013008

Other (OTH)

AF:

0.297

AC:

15321

AN:

51654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

14075

28149

42224

56298

70373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11290

22580

33870

45160

56450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.298

AC:

45348

AN:

152192

Hom.:

7241

Cov.:

AF XY:

0.299

AC XY:

22274

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.216

AC:

8992

AN:

41554

American (AMR)

AF:

0.297

AC:

4545

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

752

AN:

3466

East Asian (EAS)

AF:

0.369

AC:

1903

AN:

5160

South Asian (SAS)

AF:

0.207

AC:

1001

AN:

4830

European-Finnish (FIN)

AF:

0.432

AC:

4575

AN:

10586

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22670

AN:

67978

Other (OTH)

AF:

0.277

AC:

586

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1685

3370

5056

6741

8426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.298

Hom.:

9000

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

(source)

DANN

Benign

0.48

PhyloP100

-0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over