chr1-20685059-C-T

Variant names:

• chr1-20685059-C-T
• rs2296224
• ENST00000477167.5:n.129G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000477167.5(KIF17):​n.129G>A variant causes a non coding transcript exon 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 ENST00000477167.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 5 publications found

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]

KIF17 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.015).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF17	NM_001122819.3	c.2020-39G>A		intron_variant	Intron 9 of 14	ENST00000400463.8	NP_001116291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF17	ENST00000400463.8	c.2020-39G>A		intron_variant	Intron 9 of 14	1	NM_001122819.3	ENSP00000383311.3

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

GnomAD2 exomes AF: 0.00950 AC: 1483 AN: 156056 AF XY: 0.00931

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 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

African (AFR) AF: 0.0119 AC: 366 AN: 30834

American (AMR) AF: 0.00404 AC: 146 AN: 36094

Ashkenazi Jewish (ASJ) AF: 0.00862 AC: 215 AN: 24934

East Asian (EAS) AF: 0.0348 AC: 1246 AN: 35804

South Asian (SAS) AF: 0.00913 AC: 721 AN: 78966

European-Finnish (FIN) AF: 0.0147 AC: 718 AN: 48840

Middle Eastern (MID) AF: 0.00764 AC: 43 AN: 5630

European-Non Finnish (NFE) AF: 0.00727 AC: 7580 AN: 1043266

Other (OTH) AF: 0.00888 AC: 505 AN: 56844

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

African (AFR) AF: 0.0123 AC: 511 AN: 41574

American (AMR) AF: 0.00621 AC: 95 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

East Asian (EAS) AF: 0.0283 AC: 146 AN: 5160

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4826

European-Finnish (FIN) AF: 0.0156 AC: 166 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00719 AC: 489 AN: 67996

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00969 Hom.: 5

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
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2296224; hg19: chr1-21011552; COSMIC: COSV107214018;