17-5019897-A-G

Position:

• chr17-5019897-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The ENST00000320785.10(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 ENST00000320785.10 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24

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:):

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1C	NM_006612.6	c.1667-99A>G		intron_variant		ENST00000320785.10	NP_006603.2
KIF1C	XM_005256424.3	c.1667-99A>G		intron_variant			XP_005256481.1
KIF1C-AS1	NR_120665.2	n.145+52T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10	c.1667-99A>G		intron_variant		1	NM_006612.6	ENSP00000320821.5
KIF1C-AS1	ENST00000438266.1	n.145+52T>C		intron_variant		2
KIF1C	ENST00000573815.1	n.209-99A>G		intron_variant		5

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

Gnomad4 AFR exome AF: 0.0417

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.00328

Gnomad4 EAS exome AF: 0.0439

Gnomad4 SAS exome AF: 0.000997

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000106

Gnomad4 OTH exome AF: 0.00702

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

Gnomad4 AFR AF: 0.0427

Gnomad4 AMR AF: 0.00589

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.0532

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0114 Hom.: 6

Bravo AF: 0.0168

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs146009890; hg19: chr17-4923192;