Genetic Variant KIF18B:p.Ala841Ala (chr17-44926116-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001265577.2(KIF18B):c.2523A>G(p.Ala841Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,613,308 control chromosomes in the GnomAD database, including 73,422 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 0.35 ( 10511 hom., cov: 31)

Exomes 𝑓: 0.28 ( 62911 hom. )

Consequence

KIF18B
NM_001265577.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.13

Variant links:

Genes affected

KIF18B (HGNC:27102): (kinesin family member 18B) Enables cytoskeletal motor activity and kinesin binding activity. Involved in microtubule depolymerization; mitotic cell cycle; and regulation of cell division. Located in cytosol; microtubule; and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

KIF18B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP7

Synonymous conserved (PhyloP=-3.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF18B	NM_001265577.2 link	c.2523A>G	p.Ala841Ala	synonymous_variant	Exon 16 of 16	ENST00000593135.6	NP_001252506.1	Q86Y91-5Q6NWY8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIF18B	ENST00000593135.6 link	c.2523A>G	p.Ala841Ala	synonymous_variant	Exon 16 of 16	5	NM_001265577.2	ENSP00000465992.1	Q86Y91-5
KIF18B	ENST00000587309.5 link	c.*284A>G		3_prime_UTR_variant	Exon 15 of 15	5		ENSP00000465377.1	Q86Y91-6
KIF18B	ENST00000590129.1 link	c.*284A>G		downstream_gene_variant		1		ENSP00000465501.1	A0A494BYR6

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

52877

AN:

151656

Hom.:

10500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.546

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.180

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.337

GnomAD2 exomes

AF:

0.301

AC:

75024

AN:

249134

AF XY:

0.303

show subpopulations

Gnomad AFR exome

AF:

0.552

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.320

Gnomad EAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.179

Gnomad NFE exome

AF:

0.274

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.284

AC:

415654

AN:

1461534

Hom.:

62911

Cov.:

AF XY:

0.288

AC XY:

209177

AN XY:

727042

show subpopulations

African (AFR)

AF:

0.553

AC:

18530

AN:

33480

American (AMR)

AF:

0.323

AC:

14424

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

8425

AN:

26134

East Asian (EAS)

AF:

0.104

AC:

4114

AN:

39698

South Asian (SAS)

AF:

0.421

AC:

36328

AN:

86254

European-Finnish (FIN)

AF:

0.180

AC:

9611

AN:

53380

Middle Eastern (MID)

AF:

0.407

AC:

2348

AN:

5768

European-Non Finnish (NFE)

AF:

0.273

AC:

303856

AN:

1111742

Other (OTH)

AF:

0.298

AC:

18018

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

16982

33963

50945

67926

84908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.349

AC:

52923

AN:

151774

Hom.:

10511

Cov.:

AF XY:

0.342

AC XY:

25359

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.546

AC:

22560

AN:

41328

American (AMR)

AF:

0.292

AC:

4456

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

1163

AN:

3460

East Asian (EAS)

AF:

0.130

AC:

668

AN:

5146

South Asian (SAS)

AF:

0.416

AC:

1996

AN:

4796

European-Finnish (FIN)

AF:

0.180

AC:

1907

AN:

10566

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.280

AC:

19046

AN:

67914

Other (OTH)

AF:

0.331

AC:

698

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1583

3166

4750

6333

7916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.306

Hom.:

16428

Bravo

AF:

0.365

Asia WGS

AF:

0.281

AC:

977

AN:

3478

EpiCase

AF:

0.290

EpiControl

AF:

0.282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.30

(source)

DANN

Benign

0.47

PhyloP100

-3.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr17-44926116-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over