Variant 2-148875789-C-T 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_004522.3(KIF5C):c.126+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00736 in 1,568,610 control chromosomes in the GnomAD database, including 693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 100 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 593 hom. )

Consequence

KIF5C
NM_004522.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.476

Variant links:

Genes affected

KIF5C (HGNC:6325): (kinesin family member 5C) The protein encoded by this gene is a kinesin heavy chain subunit involved in the transport of cargo within the central nervous system. The encoded protein, which acts as a tetramer by associating with another heavy chain and two light chains, interacts with protein kinase CK2. Mutations in this gene have been associated with complex cortical dysplasia with other brain malformations-2. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Jul 2015]

KIF5C links:

KIF5C-AS1 (HGNC:40325): (KIF5C antisense RNA 1)

KIF5C-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 2-148875789-C-T is Benign according to our data. Variant chr2-148875789-C-T is described in ClinVar as [Benign]. Clinvar id is 1235352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
KIF5C	NM_004522.3 linkuse as main transcript	c.126+46C>T	intron_variant		ENST00000435030.6	NP_004513.1
KIF5C-AS1	XR_001739733.2 linkuse as main transcript	n.7529G>A	non_coding_transcript_exon_variant	4/4
KIF5C	XM_017004062.2 linkuse as main transcript	c.126+46C>T	intron_variant			XP_016859551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF5C	ENST00000435030.6 linkuse as main transcript	c.126+46C>T		intron_variant		1	NM_004522.3	ENSP00000393379	P4	O60282-1
KIF5C-AS1	ENST00000601658.5 linkuse as main transcript	n.676+1437G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0100

AC:

1527

AN:

152172

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0334

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.0237

AC:

4354

AN:

183374

Hom.:

229

AF XY:

0.0202

AC XY:

2003

AN XY:

99300

show subpopulations

Gnomad AFR exome

AF:

0.000854

Gnomad AMR exome

AF:

0.0707

Gnomad ASJ exome

AF:

0.000815

Gnomad EAS exome

AF:

0.159

Gnomad SAS exome

AF:

0.00402

Gnomad FIN exome

AF:

0.00374

Gnomad NFE exome

AF:

0.000463

Gnomad OTH exome

AF:

0.0147

GnomAD4 exome

AF:

0.00707

AC:

10017

AN:

1416330

Hom.:

593

Cov.:

AF XY:

0.00670

AC XY:

4691

AN XY:

700018

show subpopulations

Gnomad4 AFR exome

AF:

0.000493

Gnomad4 AMR exome

AF:

0.0634

Gnomad4 ASJ exome

AF:

0.000558

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.00453

Gnomad4 FIN exome

AF:

0.00441

Gnomad4 NFE exome

AF:

0.000331

Gnomad4 OTH exome

AF:

0.0115

GnomAD4 genome

AF:

0.0100

AC:

1526

AN:

152280

Hom.:

100

Cov.:

AF XY:

0.0111

AC XY:

826

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.0334

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.167

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.0134

Asia WGS

AF:

0.0530

AC:

182

AN:

3448

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	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.2

DANN

Uncertain

0.98

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