dbSNP rs12572012: KIF20B:p.Asn756Ile (chr10-89727892-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001284259.2(KIF20B):c.2267A>T(p.Asn756Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,536,074 control chromosomes in the GnomAD database, including 34,622 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 3136 hom., cov: 32)

Exomes 𝑓: 0.21 ( 31486 hom. )

Consequence

KIF20B
NM_001284259.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.336

Publications

22 publications found

Variant links:

Genes affected

KIF20B (HGNC:7212): (kinesin family member 20B) Enables several functions, including WW domain binding activity; plus-end-directed microtubule motor activity; and protein homodimerization activity. Involved in positive regulation of cell population proliferation and positive regulation of cytokinesis. Located in several cellular components, including microtubule cytoskeleton; midbody; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

KIF20B 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 (MetaRNN=0.00417462).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF20B	NM_001284259.2 link	c.2267A>T	p.Asn756Ile	missense_variant	Exon 17 of 33	ENST00000371728.8	NP_001271188.1	Q96Q89-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIF20B	ENST00000371728.8 link	c.2267A>T	p.Asn756Ile	missense_variant	Exon 17 of 33	1	NM_001284259.2	ENSP00000360793.3	Q96Q89-1
KIF20B	ENST00000260753.8 link	c.2147A>T	p.Asn716Ile	missense_variant	Exon 17 of 33	1		ENSP00000260753.4	Q96Q89-3
KIF20B	ENST00000478929.1 link	n.813A>T		non_coding_transcript_exon_variant	Exon 4 of 20	1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28116

AN:

152016

Hom.:

3139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0730

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.199

GnomAD2 exomes

AF:

0.217

AC:

51243

AN:

236060

AF XY:

0.217

show subpopulations

Gnomad AFR exome

AF:

0.0702

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.326

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.206

AC:

285294

AN:

1383938

Hom.:

31486

Cov.:

AF XY:

0.206

AC XY:

141980

AN XY:

689156

show subpopulations

African (AFR)

AF:

0.0642

AC:

2045

AN:

31852

American (AMR)

AF:

0.209

AC:

8164

AN:

39070

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

4448

AN:

24794

East Asian (EAS)

AF:

0.330

AC:

12526

AN:

37934

South Asian (SAS)

AF:

0.218

AC:

17919

AN:

82102

European-Finnish (FIN)

AF:

0.291

AC:

14774

AN:

50780

Middle Eastern (MID)

AF:

0.148

AC:

821

AN:

5566

European-Non Finnish (NFE)

AF:

0.202

AC:

213269

AN:

1054708

Other (OTH)

AF:

0.198

AC:

11328

AN:

57132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

9403

18805

28208

37610

47013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7424

14848

22272

29696

37120

<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:

0.185

AC:

28109

AN:

152136

Hom.:

3136

Cov.:

AF XY:

0.191

AC XY:

14195

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0729

AC:

3027

AN:

41534

American (AMR)

AF:

0.188

AC:

2873

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

691

AN:

3470

East Asian (EAS)

AF:

0.348

AC:

1802

AN:

5178

South Asian (SAS)

AF:

0.215

AC:

1036

AN:

4822

European-Finnish (FIN)

AF:

0.317

AC:

3334

AN:

10524

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.216

AC:

14702

AN:

67992

Other (OTH)

AF:

0.197

AC:

415

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1130

2260

3391

4521

5651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<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:

0.209

Hom.:

2593

Bravo

AF:

0.170

TwinsUK

AF:

0.227

AC:

840

ALSPAC

AF:

0.203

AC:

781

ESP6500AA

AF:

0.0723

AC:

316

ESP6500EA

AF:

0.203

AC:

1737

ExAC

AF:

0.218

AC:

26433

Asia WGS

AF:

0.271

AC:

940

AN:

3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.012

.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.48

T;T

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

2.0

.;M

PhyloP100

0.34

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.023

Sift

Benign

0.044

D;D

Sift4G

Benign

0.19

T;T

Polyphen

0.0030

B;D

Vest4

0.12

MPC

0.021

ClinPred

0.015

GERP RS

1.1

Varity_R

0.096

gMVP

0.10

Mutation Taster

=95/5

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