chr2-240733323-T-C

Variant names:

• chr2-240733323-T-C
• rs3772050
• NM_001244008.2:c.4007+3740A>G

Variant summary

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

The NM_001244008.2(KIF1A):​c.4007+3740A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 151,966 control chromosomes in the GnomAD database, including 45,315 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 0.76 (45315 hom., cov: 32)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.810

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 (AFR) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1A	NM_001244008.2	c.4007+3740A>G		intron_variant	Intron 38 of 48	ENST00000498729.9	NP_001230937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1A	ENST00000498729.9	c.4007+3740A>G		intron_variant	Intron 38 of 48	5	NM_001244008.2	ENSP00000438388.1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116139 AN: 151848 Hom.: 45271 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.765 AC: 116232 AN: 151966 Hom.: 45315 Cov.: 32 AF XY: 0.753 AC XY: 55924 AN XY: 74262

Gnomad4 AFR AF: 0.901

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.760

Alfa AF: 0.746 Hom.: 69753

Bravo AF: 0.773

Asia WGS AF: 0.584 AC: 2032 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	6.5
DANN	Benign	0.64

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: rs3772050; hg19: chr2-241672740;