rs3169733

chr17-44926116-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001265577.2(KIF18B):c.2523A>G(p.Ala841=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
KIF18B	NM_001265577.2	c.2523A>G	p.Ala841=	synonymous_variant	16/16	ENST00000593135.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF18B	ENST00000593135.6	c.2523A>G	p.Ala841=	synonymous_variant	16/16	5	NM_001265577.2	A2
KIF18B	ENST00000587309.5	c.*284A>G		3_prime_UTR_variant	15/15	5		A2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52877 AN: 151656 Hom.: 10500 Cov.: 31

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

GnomAD3 exomes AF: 0.301 AC: 75024 AN: 249134 Hom.: 12726 AF XY: 0.303 AC XY: 41021 AN XY: 135164

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 SAS exome AF: 0.426

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.: 36 AF XY: 0.288 AC XY: 209177 AN XY: 727042

Gnomad4 AFR exome AF: 0.553

Gnomad4 AMR exome AF: 0.323

Gnomad4 ASJ exome AF: 0.322

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.298

GnomAD4 genome AF: 0.349 AC: 52923 AN: 151774 Hom.: 10511 Cov.: 31 AF XY: 0.342 AC XY: 25359 AN XY: 74156

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.331

Alfa AF: 0.299 Hom.: 11821

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
Dann	Benign	0.47

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

LitVar

Other links and lift over

dbSNP: rs3169733; hg19: chr17-43003484; COSMIC: COSV59273392; COSMIC: COSV59273392;