rs148404628

Variant names:

• chr17-5020485-T-A
• rs148404628
• NM_006612.6:c.1751-7T>A

Your query was ambiguous. Multiple possible variants found:

• chr17-5020485-T-A
• chr17-5020485-T-C

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.1751-7T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0088 in 1,604,314 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0090 (73 hom.)
• Consequence: KIF1C NM_006612.6 splice_region, intron
• Scores: Splicing: ADA: 0.002009
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.408
• Publications: 1 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=-0.45).
• BP6: Variant 17-5020485-T-A is Benign according to our data. Variant chr17-5020485-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 385057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00705 (1073/152274) while in subpopulation NFE AF = 0.0111 (757/68006). AF 95% confidence interval is 0.0105. There are 9 homozygotes in GnomAd4. There are 499 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 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.1751-7T>A		splice_region 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.1751-7T>A		splice_region intron	N/A	ENSP00000320821.5	O43896
	KIF1C	ENST00000948910.1		c.1781-7T>A		splice_region intron	N/A	ENSP00000618969.1
	KIF1C	ENST00000948913.1		c.1781-7T>A		splice_region intron	N/A	ENSP00000618972.1

Frequencies

GnomAD3 genomes AF: 0.00705 AC: 1073 AN: 152156 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00699 AC: 1713 AN: 245130 AF XY: 0.00739

Gnomad AFR exome AF: 0.000809

Gnomad AMR exome AF: 0.00689

Gnomad ASJ exome AF: 0.00746

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00318

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.00898 AC: 13038 AN: 1452040 Hom.: 73 Cov.: 33 AF XY: 0.00903 AC XY: 6511 AN XY: 721122

African (AFR) AF: 0.00175 AC: 58 AN: 33206

American (AMR) AF: 0.00693 AC: 301 AN: 43462

Ashkenazi Jewish (ASJ) AF: 0.00831 AC: 213 AN: 25626

East Asian (EAS) AF: 0.00 AC: 0 AN: 39514

South Asian (SAS) AF: 0.00412 AC: 353 AN: 85716

European-Finnish (FIN) AF: 0.00265 AC: 141 AN: 53222

Middle Eastern (MID) AF: 0.0128 AC: 73 AN: 5702

European-Non Finnish (NFE) AF: 0.0103 AC: 11382 AN: 1105770

Other (OTH) AF: 0.00864 AC: 517 AN: 59822

GnomAD4 genome AF: 0.00705 AC: 1073 AN: 152274 Hom.: 9 Cov.: 32 AF XY: 0.00670 AC XY: 499 AN XY: 74456

African (AFR) AF: 0.00212 AC: 88 AN: 41550

American (AMR) AF: 0.00810 AC: 124 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4828

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0111 AC: 757 AN: 68006

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.0101 Hom.: 2

Bravo AF: 0.00736

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Hereditary spastic paraplegia (1)
-	-	1	Spastic ataxia 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	5.8
DANN	Benign	0.72
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0020
dbscSNV1_RF	Benign	0.10
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: rs148404628; hg19: chr17-4923780;