rs2296224

Positions:

• chr1-20685059-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001122819.3(KIF17):​c.2020-39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00862 in 1,513,474 control chromosomes in the GnomAD database, including 83 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 0.0099 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (73 hom.)
• Consequence: KIF17 NM_001122819.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

Genes affected

KIF17 (HGNC:19167): (kinesin family member 17) Predicted to enable microtubule binding activity and plus-end-directed microtubule motor activity. Predicted to be involved in anterograde dendritic transport of neurotransmitter receptor complex and cell projection organization. Predicted to act upstream of or within microtubule-based process; protein-containing complex localization; and vesicle-mediated transport. Predicted to be located in microtubule cytoskeleton. Predicted to be part of intraciliary transport particle B and kinesin complex. Predicted to be active in cilium; microtubule cytoskeleton; and neuron projection. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00988 (1505/152262) while in subpopulation EAS AF= 0.0283 (146/5160). AF 95% confidence interval is 0.0246. There are 10 homozygotes in gnomad4. There are 772 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF17	NM_001122819.3	c.2020-39G>A		intron_variant		ENST00000400463.8	NP_001116291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF17	ENST00000400463.8	c.2020-39G>A		intron_variant		1	NM_001122819.3	ENSP00000383311	A2

Frequencies

GnomAD3 genomes AF: 0.00987 AC: 1502 AN: 152144 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.0284

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00719

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00950 AC: 1483 AN: 156056 Hom.: 13 AF XY: 0.00931 AC XY: 776 AN XY: 83352

Gnomad AFR exome AF: 0.0124

Gnomad AMR exome AF: 0.00366

Gnomad ASJ exome AF: 0.00862

Gnomad EAS exome AF: 0.0277

Gnomad SAS exome AF: 0.00902

Gnomad FIN exome AF: 0.0148

Gnomad NFE exome AF: 0.00696

Gnomad OTH exome AF: 0.00810

GnomAD4 exome AF: 0.00848 AC: 11540 AN: 1361212 Hom.: 73 Cov.: 25 AF XY: 0.00854 AC XY: 5758 AN XY: 674532

Gnomad4 AFR exome AF: 0.0119

Gnomad4 AMR exome AF: 0.00404

Gnomad4 ASJ exome AF: 0.00862

Gnomad4 EAS exome AF: 0.0348

Gnomad4 SAS exome AF: 0.00913

Gnomad4 FIN exome AF: 0.0147

Gnomad4 NFE exome AF: 0.00727

Gnomad4 OTH exome AF: 0.00888

GnomAD4 genome AF: 0.00988 AC: 1505 AN: 152262 Hom.: 10 Cov.: 32 AF XY: 0.0104 AC XY: 772 AN XY: 74440

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.00835

Gnomad4 EAS AF: 0.0283

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0156

Gnomad4 NFE AF: 0.00719

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00938 Hom.: 4

Bravo AF: 0.00893

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.91
DANN	Benign	0.79

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

LitVar

Other links and lift over

dbSNP: rs2296224; hg19: chr1-21011552;