rs11658587

chr17-4998687-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_006612.6(KIF1C):c.-149+531C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 152,328 control chromosomes in the GnomAD database, including 53 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 0.021 (53 hom., cov: 33)
• Consequence: KIF1C NM_006612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

Genes affected

KIF1C (HGNC:6317): (kinesin family member 1C) The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. Mutations in this gene are a cause of spastic ataxia 2, autosomal recessive. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0206 (3136/152328) while in subpopulation NFE AF= 0.0332 (2261/68010). AF 95% confidence interval is 0.0321. There are 53 homozygotes in gnomad4. There are 1421 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1C	NM_006612.6	c.-149+531C>T		intron_variant		ENST00000320785.10
KIF1C	XM_005256424.3	c.-182-326C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1C	ENST00000320785.10	c.-149+531C>T		intron_variant		1	NM_006612.6	P1
KIF1C	ENST00000574165.1	c.-182-326C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 3137 AN: 152210 Hom.: 53 Cov.: 33

Gnomad AFR AF: 0.00523

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0230

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0206 AC: 3136 AN: 152328 Hom.: 53 Cov.: 33 AF XY: 0.0191 AC XY: 1421 AN XY: 74498

Gnomad4 AFR AF: 0.00522

Gnomad4 AMR AF: 0.0231

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.0332

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0288 Hom.: 16

Bravo AF: 0.0204

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	19
Dann	Benign	0.84

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: rs11658587; hg19: chr17-4901982;