chr2-240736552-G-A

Position:

• chr2-240736552-G-A

Variant summary

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

The NM_001244008.2(KIF1A):​c.4007+511C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,076 control chromosomes in the GnomAD database, including 36,759 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 0.69 (36759 hom., cov: 33)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1A	NM_001244008.2	c.4007+511C>T		intron_variant		ENST00000498729.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1A	ENST00000498729.9	c.4007+511C>T		intron_variant		5	NM_001244008.2

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105171 AN: 151958 Hom.: 36707 Cov.: 33

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.692 AC: 105281 AN: 152076 Hom.: 36759 Cov.: 33 AF XY: 0.694 AC XY: 51608 AN XY: 74340

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.839

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.720

Alfa AF: 0.664 Hom.: 47710

Bravo AF: 0.712

Asia WGS AF: 0.758 AC: 2633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.69
DANN	Benign	0.48

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: rs11886658; hg19: chr2-241675969; COSMIC: COSV57485237;