Genetic Variant NM_004521.3:c.2205-118T>C (chr10-32020077-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004521.3(KIF5B):c.2205-118T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 670,524 control chromosomes in the GnomAD database, including 90,036 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 0.47 ( 17735 hom., cov: 32)

Exomes 𝑓: 0.53 ( 72301 hom. )

Consequence

KIF5B
NM_004521.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.30

Publications

19 publications found

Variant links:

Genes affected

KIF5B (HGNC:6324): (kinesin family member 5B) Enables identical protein binding activity; microtubule binding activity; and microtubule motor activity. Involved in several processes, including lysosome localization; natural killer cell mediated cytotoxicity; and positive regulation of protein localization to plasma membrane. Located in centriolar satellite; cytosol; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

KIF5B links:

LOC107984219 (HGNC:):

LOC107984219 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 (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KIF5B	NM_004521.3 link	c.2205-118T>C	intron_variant	Intron 19 of 25	ENST00000302418.5	NP_004512.1	P33176V9HW29Q6P164
LOC107984219	XR_001747415.2 link	n.7405A>G	non_coding_transcript_exon_variant	Exon 3 of 3
KIF5B	XM_047425202.1 link	c.2205-118T>C	intron_variant	Intron 19 of 24		XP_047281158.1
KIF5B	XM_047425203.1 link	c.1923-118T>C	intron_variant	Intron 20 of 26		XP_047281159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF5B	ENST00000302418.5 link	c.2205-118T>C		intron_variant	Intron 19 of 25	1	NM_004521.3	ENSP00000307078.4		P33176
KIF5B	ENST00000493889.1 link	n.74-118T>C		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72059

AN:

151834

Hom.:

17733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.563

Gnomad AMR

AF:

0.483

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.608

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.607

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.513

Gnomad OTH

AF:

0.480

GnomAD4 exome

AF:

0.527

AC:

273497

AN:

518572

Hom.:

72301

AF XY:

0.526

AC XY:

145805

AN XY:

276950

show subpopulations

African (AFR)

AF:

0.362

AC:

4885

AN:

13488

American (AMR)

AF:

0.514

AC:

9874

AN:

19200

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

7168

AN:

14152

East Asian (EAS)

AF:

0.650

AC:

21115

AN:

32470

South Asian (SAS)

AF:

0.508

AC:

22661

AN:

44570

European-Finnish (FIN)

AF:

0.616

AC:

21752

AN:

35340

Middle Eastern (MID)

AF:

0.447

AC:

1604

AN:

3590

European-Non Finnish (NFE)

AF:

0.518

AC:

169909

AN:

327880

Other (OTH)

AF:

0.521

AC:

14529

AN:

27882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6036

12072

18108

24144

30180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1704

3408

5112

6816

8520

<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:

0.474

AC:

72085

AN:

151952

Hom.:

17735

Cov.:

AF XY:

0.479

AC XY:

35600

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.352

AC:

14567

AN:

41436

American (AMR)

AF:

0.482

AC:

7360

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.497

AC:

1726

AN:

3472

East Asian (EAS)

AF:

0.609

AC:

3142

AN:

5160

South Asian (SAS)

AF:

0.496

AC:

2388

AN:

4810

European-Finnish (FIN)

AF:

0.607

AC:

6394

AN:

10526

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.513

AC:

34851

AN:

67970

Other (OTH)

AF:

0.478

AC:

1007

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1906

3812

5719

7625

9531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<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:

0.495

Hom.:

55600

Bravo

AF:

0.460

Asia WGS

AF:

0.516

AC:

1792

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.50

(source)

DANN

Benign

0.38

PhyloP100

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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