chr17-5020462-G-A

Variant names:

• chr17-5020462-G-A
• rs28600139
• NM_006612.6:c.1751-30G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006612.6(KIF1C):​c.1751-30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 1,583,604 control chromosomes in the GnomAD database, including 1,893 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.064 (473 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1420 hom.)
• Consequence: KIF1C NM_006612.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.06
• Publications: 2 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 -20 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-5020462-G-A is Benign according to our data. Variant chr17-5020462-G-A is described in ClinVar as Benign. ClinVar VariationId is 1237107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	NM_006612.6	MANE Select	c.1751-30G>A		intron	N/A	NP_006603.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	ENST00000320785.10	TSL:1 MANE Select	c.1751-30G>A		intron	N/A	ENSP00000320821.5	O43896
	KIF1C	ENST00000948910.1		c.1781-30G>A		intron	N/A	ENSP00000618969.1
	KIF1C	ENST00000948913.1		c.1781-30G>A		intron	N/A	ENSP00000618972.1

Frequencies

GnomAD3 genomes AF: 0.0635 AC: 9662 AN: 152104 Hom.: 474 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0300

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.00694

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0569

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0382

Gnomad OTH AF: 0.0575

GnomAD2 exomes AF: 0.0372 AC: 8583 AN: 230796 AF XY: 0.0347

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.0211

Gnomad ASJ exome AF: 0.0197

Gnomad EAS exome AF: 0.00702

Gnomad FIN exome AF: 0.0561

Gnomad NFE exome AF: 0.0361

Gnomad OTH exome AF: 0.0361

GnomAD4 exome AF: 0.0400 AC: 57279 AN: 1431382 Hom.: 1420 Cov.: 31 AF XY: 0.0389 AC XY: 27578 AN XY: 708852

African (AFR) AF: 0.136 AC: 4429 AN: 32682

American (AMR) AF: 0.0212 AC: 881 AN: 41480

Ashkenazi Jewish (ASJ) AF: 0.0197 AC: 478 AN: 24272

East Asian (EAS) AF: 0.00292 AC: 115 AN: 39320

South Asian (SAS) AF: 0.0105 AC: 877 AN: 83276

European-Finnish (FIN) AF: 0.0567 AC: 2973 AN: 52448

Middle Eastern (MID) AF: 0.0188 AC: 106 AN: 5630

European-Non Finnish (NFE) AF: 0.0412 AC: 45006 AN: 1093460

Other (OTH) AF: 0.0410 AC: 2414 AN: 58814

GnomAD4 genome AF: 0.0635 AC: 9667 AN: 152222 Hom.: 473 Cov.: 32 AF XY: 0.0628 AC XY: 4673 AN XY: 74438

African (AFR) AF: 0.137 AC: 5691 AN: 41512

American (AMR) AF: 0.0299 AC: 458 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.00696 AC: 36 AN: 5174

South Asian (SAS) AF: 0.0108 AC: 52 AN: 4828

European-Finnish (FIN) AF: 0.0569 AC: 605 AN: 10628

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0382 AC: 2598 AN: 67994

Other (OTH) AF: 0.0578 AC: 122 AN: 2110

Alfa AF: 0.0710 Hom.: 236

Bravo AF: 0.0647

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.85
CADD	Benign	0.11
DANN	Benign	0.45
PhyloP100		-2.1
BranchPoint Hunter		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs28600139; hg19: chr17-4923757;