Genetic Variant KIF5B:c.-444A>G (chr10-32056417-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_004521.3(KIF5B):c.-444A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 162,730 control chromosomes in the GnomAD database, including 5,492 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 0.26 ( 5251 hom., cov: 33)

Exomes 𝑓: 0.18 ( 241 hom. )

Consequence

KIF5B
NM_004521.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.192

Publications

1 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:

Genome browser will be placed here

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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KIF5B	NM_004521.3 link	c.-444A>G	5_prime_UTR_variant	Exon 1 of 26	ENST00000302418.5	NP_004512.1	P33176V9HW29Q6P164
KIF5B	XM_047425202.1 link	c.-444A>G	5_prime_UTR_variant	Exon 1 of 25		XP_047281158.1
KIF5B	XM_047425203.1 link	c.-940A>G	5_prime_UTR_variant	Exon 1 of 27		XP_047281159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF5B	ENST00000302418.5 link	c.-444A>G		5_prime_UTR_variant	Exon 1 of 26	1	NM_004521.3	ENSP00000307078.4		P33176

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39475

AN:

151932

Hom.:

5244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.386

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.241

Gnomad OTH

AF:

0.265

GnomAD4 exome

AF:

0.177

AC:

1888

AN:

10682

Hom.:

241

Cov.:

AF XY:

0.184

AC XY:

1058

AN XY:

5762

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.185

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

AN:

234

East Asian (EAS)

AF:

0.300

AC:

AN:

South Asian (SAS)

AF:

0.223

AC:

565

AN:

2528

European-Finnish (FIN)

AF:

0.142

AC:

AN:

678

Middle Eastern (MID)

AF:

0.271

AC:

AN:

European-Non Finnish (NFE)

AF:

0.161

AC:

1032

AN:

6422

Other (OTH)

AF:

0.165

AC:

104

AN:

632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

136

204

272

340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.260

AC:

39493

AN:

152048

Hom.:

5251

Cov.:

AF XY:

0.261

AC XY:

19408

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.262

AC:

10873

AN:

41526

American (AMR)

AF:

0.309

AC:

4722

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

927

AN:

3470

East Asian (EAS)

AF:

0.385

AC:

1973

AN:

5122

South Asian (SAS)

AF:

0.324

AC:

1562

AN:

4822

European-Finnish (FIN)

AF:

0.209

AC:

2210

AN:

10594

Middle Eastern (MID)

AF:

0.281

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.241

AC:

16350

AN:

67926

Other (OTH)

AF:

0.265

AC:

559

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1540

3080

4621

6161

7701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.139

Hom.:

256

Bravo

AF:

0.264

Asia WGS

AF:

0.346

AC:

1204

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.3

(source)

DANN

Benign

0.40

PhyloP100

-0.19

PromoterAI

0.046

Neutral

(source)

Mutation Taster

=300/0

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