Variant 10-32023041-A-G 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_004521.3(KIF5B):c.1726-5T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,517,138 control chromosomes in the GnomAD database, including 751,326 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 72325 hom., cov: 32)

Exomes 𝑓: 1.0 ( 679001 hom. )

Consequence

KIF5B
NM_004521.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001508

Clinical Significance

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

Conservation

PhyloP100: 0.221

Variant links:

Genes affected

KIF5B (HGNC:6324): (kinesin family member 5B) Enables identical protein binding activity; microtubule binding activity; and microtubule motor activity. Involved in several processes, including lysosome localization; natural killer cell mediated cytotoxicity; and positive regulation of protein localization to plasma membrane. Located in centriolar satellite; cytosol; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

KIF5B 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=-0.84).

BP6

Variant 10-32023041-A-G is Benign according to our data. Variant chr10-32023041-A-G is described in ClinVar as [Benign]. Clinvar id is 1302449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
KIF5B	NM_004521.3 linkuse as main transcript	c.1726-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000302418.5	NP_004512.1
KIF5B	XM_047425202.1 linkuse as main transcript	c.1726-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		XP_047281158.1
KIF5B	XM_047425203.1 linkuse as main transcript	c.1444-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		XP_047281159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF5B	ENST00000302418.5 linkuse as main transcript	c.1726-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004521.3	ENSP00000307078	P1

Frequencies

GnomAD3 genomes

AF:

0.974

AC:

148178

AN:

152170

Hom.:

72272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.909

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.991

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.977

GnomAD3 exomes

AF:

0.993

AC:

224053

AN:

225668

Hom.:

111293

AF XY:

0.995

AC XY:

122069

AN XY:

122706

show subpopulations

Gnomad AFR exome

AF:

0.904

Gnomad AMR exome

AF:

0.995

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.997

GnomAD4 exome

AF:

0.997

AC:

1361250

AN:

1364850

Hom.:

679001

Cov.:

AF XY:

0.998

AC XY:

672504

AN XY:

674020

show subpopulations

Gnomad4 AFR exome

AF:

0.904

Gnomad4 AMR exome

AF:

0.995

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.995

GnomAD4 genome

AF:

0.974

AC:

148290

AN:

152288

Hom.:

72325

Cov.:

AF XY:

0.974

AC XY:

72563

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.909

Gnomad4 AMR

AF:

0.991

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.978

Alfa

AF:

0.993

Hom.:

25764

Bravo

AF:

0.970

Asia WGS

AF:

0.995

AC:

3461

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	Oct 28, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.6

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.030

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