Variant 2-240741227-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001244008.2(KIF1A):c.3749+42C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,377,184 control chromosomes in the GnomAD database, including 50,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6151 hom., cov: 33)

Exomes 𝑓: 0.26 ( 43875 hom. )

Consequence

KIF1A
NM_001244008.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.290

Variant links:

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 links:

KIF1A (HGNC:):

KIF1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-240741227-G-C is Benign according to our data. Variant chr2-240741227-G-C is described in ClinVar as [Benign]. Clinvar id is 674046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240741227-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1A	NM_001244008.2 linkuse as main transcript	c.3749+42C>G		intron_variant		ENST00000498729.9	NP_001230937.1	Q12756-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1A	ENST00000498729.9 linkuse as main transcript	c.3749+42C>G		intron_variant		5	NM_001244008.2	ENSP00000438388.1		Q12756-3

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41991

AN:

151888

Hom.:

6136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.0637

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.287

GnomAD3 exomes

AF:

0.228

AC:

34202

AN:

149950

Hom.:

4552

AF XY:

0.229

AC XY:

18329

AN XY:

80132

show subpopulations

Gnomad AFR exome

AF:

0.332

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.0664

Gnomad SAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.256

Gnomad NFE exome

AF:

0.275

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

AF:

0.262

AC:

320434

AN:

1225178

Hom.:

43875

Cov.:

AF XY:

0.259

AC XY:

158719

AN XY:

612574

show subpopulations

Gnomad4 AFR exome

AF:

0.341

Gnomad4 AMR exome

AF:

0.150

Gnomad4 ASJ exome

AF:

0.345

Gnomad4 EAS exome

AF:

0.0535

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.272

Gnomad4 NFE exome

AF:

0.276

Gnomad4 OTH exome

AF:

0.254

GnomAD4 genome

AF:

0.277

AC:

42039

AN:

152006

Hom.:

6151

Cov.:

AF XY:

0.272

AC XY:

20216

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.338

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.350

Gnomad4 EAS

AF:

0.0634

Gnomad4 SAS

AF:

0.172

Gnomad4 FIN

AF:

0.261

Gnomad4 NFE

AF:

0.275

Gnomad4 OTH

AF:

0.285

Alfa

AF:

0.205

Hom.:

676

Bravo

AF:

0.276

Asia WGS

AF:

0.122

AC:

429

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.28

DANN

Benign

0.34

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over