NM_001244008.2:c.4007+3740A>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

KIF1A Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 9

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neuropathy, hereditary sensory, type 2C

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• hereditary spastic paraplegia 30

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• PEHO syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary sensory and autonomic neuropathy type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244008.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1A	NM_001244008.2	MANE Select	c.4007+3740A>G		intron	N/A	NP_001230937.1
	KIF1A	NM_001379631.1		c.4082+3740A>G		intron	N/A	NP_001366560.1
	KIF1A	NM_001379642.1		c.4007+1396A>G		intron	N/A	NP_001366571.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1A	ENST00000498729.9	TSL:5 MANE Select	c.4007+3740A>G		intron	N/A	ENSP00000438388.1
	KIF1A	ENST00000492812.6	TSL:1	n.1169+3740A>G		intron	N/A
	KIF1A	ENST00000675932.2		c.4007+3740A>G		intron	N/A	ENSP00000502786.2

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

African (AFR) AF: 0.901 AC: 37330 AN: 41454

American (AMR) AF: 0.657 AC: 10047 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2700 AN: 3470

East Asian (EAS) AF: 0.673 AC: 3460 AN: 5144

South Asian (SAS) AF: 0.517 AC: 2484 AN: 4808

European-Finnish (FIN) AF: 0.647 AC: 6834 AN: 10568

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50786 AN: 67906

Other (OTH) AF: 0.760 AC: 1603 AN: 2108

Alfa AF: 0.753 Hom.: 125592

Bravo AF: 0.773

Asia WGS AF: 0.584 AC: 2032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.5
DANN	Benign	0.64
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3772050; hg19: chr2-241672740;