rs7576602

Positions:

• chr2-240745275-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001244008.2(KIF1A):​c.3465+152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,144 control chromosomes in the GnomAD database, including 2,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.16 (2245 hom., cov: 33)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.244

Genes affected

KIF1A (HGNC:888): (kinesin family member 1A) The protein encoded by this gene is a member of the kinesin family and functions as an anterograde motor protein that transports membranous organelles along axonal microtubules. Mutations at this locus have been associated with spastic paraplegia-30 and hereditary sensory neuropathy IIC. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-240745275-C-T is Benign according to our data. Variant chr2-240745275-C-T is described in ClinVar as [Benign]. Clinvar id is 1281671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1A	NM_001244008.2	c.3465+152G>A		intron_variant		ENST00000498729.9	NP_001230937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1A	ENST00000498729.9	c.3465+152G>A		intron_variant		5	NM_001244008.2	ENSP00000438388

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24187 AN: 152028 Hom.: 2244 Cov.: 33

Gnomad AFR AF: 0.0714

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.0785

Gnomad SAS AF: 0.0897

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.159 AC: 24194 AN: 152144 Hom.: 2245 Cov.: 33 AF XY: 0.157 AC XY: 11642 AN XY: 74372

Gnomad4 AFR AF: 0.0713

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.0787

Gnomad4 SAS AF: 0.0912

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.186

Alfa AF: 0.176 Hom.: 400

Bravo AF: 0.154

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs7576602; hg19: chr2-241684692;