Genetic Variant NM_001394837.1:c.1848+3501G>A (chr14-103695926-G-A) – 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+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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.682

Publications

14 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=-0.91).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KLC1	NM_001394837.1	MANE Select	c.1848+3501G>A	intron	N/A	NP_001381766.1	Q07866-9
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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KLC1	ENST00000334553.11	TSL:5 MANE Select	c.1848+3501G>A	intron	N/A	ENSP00000334523.6	Q07866-9
KLC1	ENST00000348520.10	TSL:1	c.1651-4729G>A	intron	N/A	ENSP00000341154.6	Q07866-1
KLC1	ENST00000881698.1		c.1923+3501G>A	intron	N/A	ENSP00000551757.1

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91668

AN:

151938

Hom.:

28592

Cov.:

show subpopulations

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.:

AF XY:

0.675

AC XY:

259834

AN XY:

384698

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

10148

20297

30445

40594

50742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18200

36400

54600

72800

91000

<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:

0.603

AC:

91732

AN:

152056

Hom.:

28616

Cov.:

AF XY:

0.598

AC XY:

44479

AN XY:

74340

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1786

3573

5359

7146

8932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.631

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

(source)

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)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over