Genetic Variant NM_004521.3: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:

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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=-0.81).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004521.3. 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
	KIF5B	NM_004521.3	MANE Select	c.-444A>G		5_prime_UTR	Exon 1 of 26	NP_004512.1	P33176

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIF5B	ENST00000302418.5	TSL:1 MANE Select	c.-444A>G	5_prime_UTR	Exon 1 of 26	ENSP00000307078.4	P33176
KIF5B	ENST00000861448.1		c.-444A>G	5_prime_UTR	Exon 1 of 26	ENSP00000531507.1
KIF5B	ENST00000948543.1		c.-444A>G	5_prime_UTR	Exon 1 of 25	ENSP00000618602.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over