Variant rs75876570 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004523.4(KIF11):c.2771-6T>A 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 0.00537 in 1,588,138 control chromosomes in the GnomAD database, including 43 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 40 hom. )

Consequence

KIF11
NM_004523.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.04179

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.160

Variant links:

Genes affected

KIF11 (HGNC:6388): (kinesin family member 11) This gene encodes a motor protein that belongs to the kinesin-like protein family. Members of this protein family are known to be involved in various kinds of spindle dynamics. The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis. [provided by RefSeq, Jul 2008]

KIF11 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=-0.8).

BP6

Variant 10-92649829-T-A is Benign according to our data. Variant chr10-92649829-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 211273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-92649829-T-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00546 (7845/1435868) while in subpopulation MID AF= 0.0183 (104/5684). AF 95% confidence interval is 0.0154. There are 40 homozygotes in gnomad4_exome. There are 3921 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High AC in GnomAd4 at 682 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF11	NM_004523.4 linkuse as main transcript	c.2771-6T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000260731.5	NP_004514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF11	ENST00000260731.5 linkuse as main transcript	c.2771-6T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004523.4	ENSP00000260731	P1

Frequencies

GnomAD3 genomes

AF:

0.00448

AC:

682

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00798

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00583

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00494

AC:

1219

AN:

246914

Hom.:

AF XY:

0.00528

AC XY:

704

AN XY:

133442

show subpopulations

Gnomad AFR exome

AF:

0.000807

Gnomad AMR exome

AF:

0.00463

Gnomad ASJ exome

AF:

0.0137

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00439

Gnomad FIN exome

AF:

0.000556

Gnomad NFE exome

AF:

0.00657

Gnomad OTH exome

AF:

0.00632

GnomAD4 exome

AF:

0.00546

AC:

7845

AN:

1435868

Hom.:

Cov.:

AF XY:

0.00551

AC XY:

3921

AN XY:

711722

show subpopulations

Gnomad4 AFR exome

AF:

0.00112

Gnomad4 AMR exome

AF:

0.00450

Gnomad4 ASJ exome

AF:

0.0139

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00448

Gnomad4 FIN exome

AF:

0.000888

Gnomad4 NFE exome

AF:

0.00578

Gnomad4 OTH exome

AF:

0.00695

GnomAD4 genome

AF:

0.00448

AC:

682

AN:

152270

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

343

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.00797

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00436

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.00584

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.00701

Hom.:

Bravo

AF:

0.00451

Asia WGS

AF:

0.00347

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	KIF11: BP4, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 11, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.7

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.042

dbscSNV1_RF

Benign

0.42

SpliceAI score (max)

0.010

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