1-20684689-G-A

Variant names:

• chr1-20684689-G-A
• rs2296223
• NM_001122819.3:c.2231+120C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001122819.3(KIF17):​c.2231+120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 1,020,942 control chromosomes in the GnomAD database, including 3,765 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 0.086 (860 hom., cov: 33)
  • Exomes 𝑓: 0.062 (2905 hom.)
• Consequence: KIF17 NM_001122819.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71
• Publications: 4 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 (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122819.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF17	NM_001122819.3	MANE Select	c.2231+120C>T		intron	N/A	NP_001116291.1
	KIF17	NM_020816.4		c.2231+120C>T		intron	N/A	NP_065867.2
	KIF17	NM_001287212.2		c.1931+120C>T		intron	N/A	NP_001274141.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF17	ENST00000400463.8	TSL:1 MANE Select	c.2231+120C>T		intron	N/A	ENSP00000383311.3
	KIF17	ENST00000247986.2	TSL:1	c.2231+120C>T		intron	N/A	ENSP00000247986.2
	KIF17	ENST00000375044.5	TSL:1	c.1931+120C>T		intron	N/A	ENSP00000364184.1

Frequencies

GnomAD3 genomes AF: 0.0855 AC: 13002 AN: 152124 Hom.: 856 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0920

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.0764

Gnomad FIN AF: 0.0321

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0466

Gnomad OTH AF: 0.0813

GnomAD4 exome AF: 0.0621 AC: 53970 AN: 868700 Hom.: 2905 AF XY: 0.0614 AC XY: 27181 AN XY: 442880

African (AFR) AF: 0.142 AC: 3035 AN: 21444

American (AMR) AF: 0.0865 AC: 2930 AN: 33886

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 415 AN: 19918

East Asian (EAS) AF: 0.292 AC: 9701 AN: 33180

South Asian (SAS) AF: 0.0667 AC: 4215 AN: 63176

European-Finnish (FIN) AF: 0.0337 AC: 1136 AN: 33680

Middle Eastern (MID) AF: 0.0544 AC: 161 AN: 2958

European-Non Finnish (NFE) AF: 0.0474 AC: 29412 AN: 619966

Other (OTH) AF: 0.0732 AC: 2965 AN: 40492

GnomAD4 genome AF: 0.0855 AC: 13023 AN: 152242 Hom.: 860 Cov.: 33 AF XY: 0.0866 AC XY: 6446 AN XY: 74446

African (AFR) AF: 0.137 AC: 5680 AN: 41516

American (AMR) AF: 0.0925 AC: 1416 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3470

East Asian (EAS) AF: 0.340 AC: 1757 AN: 5168

South Asian (SAS) AF: 0.0773 AC: 373 AN: 4828

European-Finnish (FIN) AF: 0.0321 AC: 341 AN: 10624

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0466 AC: 3169 AN: 68004

Other (OTH) AF: 0.0799 AC: 169 AN: 2114

Alfa AF: 0.0520 Hom.: 308

Bravo AF: 0.0945

Asia WGS AF: 0.199 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.25
DANN	Benign	0.36
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs2296223; hg19: chr1-21011182;