2-240802560-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.-60-4748G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,010 control chromosomes in the GnomAD database, including 18,986 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 0.47 (18986 hom., cov: 32)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1A	NM_001244008.2	c.-60-4748G>A		intron_variant		ENST00000498729.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1A	ENST00000498729.9	c.-60-4748G>A		intron_variant		5	NM_001244008.2

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71703 AN: 151890 Hom.: 18939 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.472 AC: 71797 AN: 152010 Hom.: 18986 Cov.: 32 AF XY: 0.471 AC XY: 34994 AN XY: 74294

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.440

Alfa AF: 0.370 Hom.: 10551

Bravo AF: 0.481

Asia WGS AF: 0.477 AC: 1665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.097
Dann	Benign	0.35

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: rs7599943; hg19: chr2-241741977;