rs238237

Variant names:

• chr17-4999663-G-A
• rs238237
• NM_006612.6:c.-148-187G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006612.6(KIF1C):​c.-148-187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,034 control chromosomes in the GnomAD database, including 48,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.79 (48759 hom., cov: 31)
• Consequence: KIF1C NM_006612.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.48
• Publications: 7 publications found

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]

KIF1C Gene-Disease associations (from GenCC):

• spastic ataxia 2

  Inheritance: AR, AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 17-4999663-G-A is Benign according to our data. Variant chr17-4999663-G-A is described in ClinVar as Benign. ClinVar VariationId is 1526316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006612.6. 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
	KIF1C	NM_006612.6	MANE Select	c.-148-187G>A		intron	N/A	NP_006603.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	ENST00000320785.10	TSL:1 MANE Select	c.-148-187G>A		intron	N/A	ENSP00000320821.5
	KIF1C	ENST00000574165.1	TSL:5	c.-148-187G>A		intron	N/A	ENSP00000458697.1

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120582 AN: 151916 Hom.: 48708 Cov.: 31

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.794 AC: 120696 AN: 152034 Hom.: 48759 Cov.: 31 AF XY: 0.782 AC XY: 58085 AN XY: 74292

African (AFR) AF: 0.911 AC: 37774 AN: 41484

American (AMR) AF: 0.736 AC: 11249 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2500 AN: 3470

East Asian (EAS) AF: 0.477 AC: 2458 AN: 5158

South Asian (SAS) AF: 0.503 AC: 2422 AN: 4814

European-Finnish (FIN) AF: 0.701 AC: 7399 AN: 10550

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54294 AN: 67968

Other (OTH) AF: 0.810 AC: 1705 AN: 2104

Alfa AF: 0.788 Hom.: 16225

Bravo AF: 0.805

Asia WGS AF: 0.540 AC: 1881 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.56
PhyloP100		1.5
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: rs238237; hg19: chr17-4902958; COSMIC: COSV57903586; COSMIC: COSV57903586;