dbSNP rs3732341: KIF1A:c.*1237C>T (chr2-240716127-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001244008.2(KIF1A):c.*1237C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,770 control chromosomes in the GnomAD database, including 12,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 12148 hom., cov: 30)

Exomes 𝑓: 0.43 ( 18 hom. )

Consequence

KIF1A
NM_001244008.2 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.00200

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:

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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=-0.9).

BP6

Variant 2-240716127-G-A is Benign according to our data. Variant chr2-240716127-G-A is described in ClinVar as [Benign]. Clinvar id is 335240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1A	NM_001244008.2 link	c.*1237C>T		3_prime_UTR_variant	Exon 49 of 49	ENST00000498729.9	NP_001230937.1	Q12756-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1A	ENST00000498729 link	c.*1237C>T		3_prime_UTR_variant	Exon 49 of 49	5	NM_001244008.2	ENSP00000438388.1		Q12756-3

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56029

AN:

151474

Hom.:

12144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.455

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.420

GnomAD4 exome

AF:

0.426

AC:

AN:

176

Hom.:

Cov.:

AF XY:

0.464

AC XY:

AN XY:

112

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.395

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.625

Gnomad4 NFE exome

AF:

0.516

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.370

AC:

56045

AN:

151594

Hom.:

12148

Cov.:

AF XY:

0.368

AC XY:

27241

AN XY:

74054

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.406

Gnomad4 ASJ

AF:

0.554

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.272

Gnomad4 FIN

AF:

0.455

Gnomad4 NFE

AF:

0.483

Gnomad4 OTH

AF:

0.417

Alfa

AF:

0.448

Hom.:

9844

Bravo

AF:

0.359

Asia WGS

AF:

0.232

AC:

805

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hereditary spastic paraplegia 30

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.3

DANN

Benign

0.56

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