rs6732174

chr2-240792123-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001244008.2(KIF1A):c.107-2811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,934 control chromosomes in the GnomAD database, including 4,806 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (4806 hom., cov: 31)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1A	NM_001244008.2	c.107-2811G>A		intron_variant		ENST00000498729.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1A	ENST00000498729.9	c.107-2811G>A		intron_variant		5	NM_001244008.2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37590 AN: 151816 Hom.: 4804 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.247 AC: 37586 AN: 151934 Hom.: 4806 Cov.: 31 AF XY: 0.246 AC XY: 18263 AN XY: 74256

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.239

Alfa AF: 0.268 Hom.: 906

Bravo AF: 0.235

Asia WGS AF: 0.177 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.75

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: rs6732174; hg19: chr2-241731540;