chr17-5019897-A-G

Variant names:

• chr17-5019897-A-G
• rs146009890
• NM_006612.6:c.1667-99A>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_006612.6(KIF1C):​c.1667-99A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00585 in 828,922 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (44 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (56 hom.)
• Consequence: KIF1C NM_006612.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24
• Publications: 0 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-AS1 (HGNC:40324): (KIF1C antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 17-5019897-A-G is Benign according to our data. Variant chr17-5019897-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1196048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0145 (2206/152070) while in subpopulation EAS AF = 0.0532 (275/5168). AF 95% confidence interval is 0.048. There are 44 homozygotes in GnomAd4. There are 1049 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 44 AR,AD gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	NM_006612.6	MANE Select	c.1667-99A>G		intron	N/A	NP_006603.2
	KIF1C-AS1	NR_120665.2		n.145+52T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	ENST00000320785.10	TSL:1 MANE Select	c.1667-99A>G		intron	N/A	ENSP00000320821.5	O43896
	KIF1C	ENST00000948910.1		c.1697-99A>G		intron	N/A	ENSP00000618969.1
	KIF1C	ENST00000948913.1		c.1697-99A>G		intron	N/A	ENSP00000618972.1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2195 AN: 151952 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00590

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0535

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0106

GnomAD4 exome AF: 0.00390 AC: 2640 AN: 676852 Hom.: 56 Cov.: 9 AF XY: 0.00348 AC XY: 1244 AN XY: 357356

African (AFR) AF: 0.0417 AC: 735 AN: 17626

American (AMR) AF: 0.00197 AC: 68 AN: 34456

Ashkenazi Jewish (ASJ) AF: 0.00328 AC: 66 AN: 20106

East Asian (EAS) AF: 0.0439 AC: 1419 AN: 32340

South Asian (SAS) AF: 0.000997 AC: 64 AN: 64194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48380

Middle Eastern (MID) AF: 0.00150 AC: 4 AN: 2672

European-Non Finnish (NFE) AF: 0.000106 AC: 45 AN: 423026

Other (OTH) AF: 0.00702 AC: 239 AN: 34052

GnomAD4 genome AF: 0.0145 AC: 2206 AN: 152070 Hom.: 44 Cov.: 32 AF XY: 0.0141 AC XY: 1049 AN XY: 74334

African (AFR) AF: 0.0427 AC: 1771 AN: 41458

American (AMR) AF: 0.00589 AC: 90 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3468

East Asian (EAS) AF: 0.0532 AC: 275 AN: 5168

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67968

Other (OTH) AF: 0.0114 AC: 24 AN: 2106

Alfa AF: 0.0130 Hom.: 7

Bravo AF: 0.0168

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.86
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs146009890; hg19: chr17-4923192;