rs1678542

Positions:

• chr12-57574932-C-G
• chr12-57574932-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000455537.7(KIF5A):​c.1717-152C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 707,348 control chromosomes in the GnomAD database, including 71,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (14219 hom., cov: 30)
  • Exomes 𝑓: 0.44 (57361 hom.)
• Consequence: KIF5A ENST00000455537.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.211

Genes affected

KIF5A (HGNC:6323): (kinesin family member 5A) This gene encodes a member of the kinesin family of proteins. Members of this family are part of a multisubunit complex that functions as a microtubule motor in intracellular organelle transport. Mutations in this gene cause autosomal dominant spastic paraplegia 10. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 12-57574932-C-G is Benign according to our data. Variant chr12-57574932-C-G is described in ClinVar as [Benign]. Clinvar id is 682870.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF5A	NM_004984.4	c.1717-152C>G		intron_variant		ENST00000455537.7	NP_004975.2
KIF5A	NM_001354705.2	c.1450-152C>G		intron_variant			NP_001341634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF5A	ENST00000455537.7	c.1717-152C>G		intron_variant		1	NM_004984.4	ENSP00000408979	P1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64352 AN: 151842 Hom.: 14181 Cov.: 30

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.436 AC: 241959 AN: 555388 Hom.: 57361 AF XY: 0.442 AC XY: 131285 AN XY: 297040

Gnomad4 AFR exome AF: 0.424

Gnomad4 AMR exome AF: 0.501

Gnomad4 ASJ exome AF: 0.372

Gnomad4 EAS exome AF: 0.790

Gnomad4 SAS exome AF: 0.587

Gnomad4 FIN exome AF: 0.511

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.425

GnomAD4 genome AF: 0.424 AC: 64444 AN: 151960 Hom.: 14219 Cov.: 30 AF XY: 0.436 AC XY: 32389 AN XY: 74264

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.401

Alfa AF: 0.395 Hom.: 6953

Bravo AF: 0.417

Asia WGS AF: 0.657 AC: 2284 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.97
CADD	Benign	3.6
DANN	Benign	0.26

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: rs1678542; hg19: chr12-57968715;