rs1678542

Variant names:

Your query was ambiguous. Multiple possible variants found:

Germline classification Cancer classification (beta)

Variant summary

Our verdict is . The variant received -14 ACMG points: 0P and 14B. BA1BP4_StrongBP6_Moderate

The NM_004984.4(KIF5A):c.1717-152C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.433 (AC=306,403) in the gnomAD database across 707,348 control chromosomes, including 71,580 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.782. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★).

Frequency

Genomes: 𝑓 0.42 ( 14219 hom., cov: 30)

Exomes 𝑓: 0.44 ( 57361 hom. )

Consequence

KIF5A
NM_004984.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.211

Publications

79 publications found

Variant links:

Genes affected

KIF5A (HGNC:6323): (kinesin family member 5A) This gene encodes a member of the kinesin family of proteins. Members of this family are part of a multisubunit complex that functions as a microtubule motor in intracellular organelle transport. Mutations in this gene cause autosomal dominant spastic paraplegia 10. [provided by RefSeq, Jul 2008]

KIF5A Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis, susceptibility to, 25
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Illumina, ClinGen
inherited neurodegenerative disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
myoclonus, intractable, neonatal
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, Illumina, G2P, Labcorp Genetics (formerly Invitae)
hereditary spastic paraplegia 10
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KIF5A links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004984.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BP6

ClinVar 1-star benign — moderate (BP6); ClinVar germline classification: Benign/Likely Benign, 1 star(s).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.7821 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004984.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5A	NM_004984.4	MANE Select	c.1717-152C>G		intron	N/A	NP_004975.2
	KIF5A	NM_001354705.2		c.1450-152C>G		intron	N/A	NP_001341634.1	J3KNA1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIF5A	ENST00000455537.7	TSL:1 MANE Select	c.1717-152C>G	intron	N/A	ENSP00000408979.2	Q12840
KIF5A	ENST00000674619.1		c.1717-152C>G	intron	N/A	ENSP00000502270.1	A0A6Q8PGJ3
KIF5A	ENST00000938849.1		c.1717-152C>G	intron	N/A	ENSP00000608908.1

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64352

AN:

151842

Hom.:

14181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.511

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.772

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.395

GnomAD4 exome

AF:

0.436

AC:

241959

AN:

555388

Hom.:

57361

AF XY:

0.442

AC XY:

131285

AN XY:

297040

show subpopulations

African (AFR)

AF:

0.424

AC:

6547

AN:

15448

American (AMR)

AF:

0.501

AC:

15905

AN:

31778

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

6853

AN:

18406

East Asian (EAS)

AF:

0.790

AC:

25132

AN:

31802

South Asian (SAS)

AF:

0.587

AC:

34126

AN:

58180

European-Finnish (FIN)

AF:

0.511

AC:

19453

AN:

38100

Middle Eastern (MID)

AF:

0.335

AC:

818

AN:

2444

European-Non Finnish (NFE)

AF:

0.366

AC:

120307

AN:

329044

Other (OTH)

AF:

0.425

AC:

12818

AN:

30186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6804

13608

20412

27216

34020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1060

2120

3180

4240

5300

<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:

0.424

AC:

64444

AN:

151960

Hom.:

14219

Cov.:

AF XY:

0.436

AC XY:

32389

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.421

AC:

17428

AN:

41420

American (AMR)

AF:

0.439

AC:

6709

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

1274

AN:

3464

East Asian (EAS)

AF:

0.771

AC:

3984

AN:

5166

South Asian (SAS)

AF:

0.606

AC:

2914

AN:

4812

European-Finnish (FIN)

AF:

0.537

AC:

5658

AN:

10546

Middle Eastern (MID)

AF:

0.284

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.369

AC:

25082

AN:

67952

Other (OTH)

AF:

0.401

AC:

846

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1888

3776

5664

7552

9440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<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:

0.395

Hom.:

6953

Bravo

AF:

0.417

Asia WGS

AF:

0.657

AC:

2284

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.798

AC:

97993

AN:

122762

Turkish Variome

AF:

0.407

AC:

629

AN:

1546

Hom.:

140

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.768

AC:

6881

AN:

8960

Hom.:

2650

ABraOM SABE-WGS-1171

AF:

0.402

AC:

941

AN:

2342

Hom.:

192

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.6

(source)

DANN

Benign

0.26

PhyloP100

0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over