chr10-92607473-A-G

Variant names:

• chr10-92607473-A-G
• rs10786050
• NM_004523.4:c.387+236A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004523.4(KIF11):​c.387+236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,048 control chromosomes in the GnomAD database, including 38,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.70 (38549 hom., cov: 31)
• Consequence: KIF11 NM_004523.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 10-92607473-A-G is Benign according to our data. Variant chr10-92607473-A-G is described in ClinVar as Benign. ClinVar VariationId is 1266516.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF11	NM_004523.4	c.387+236A>G		intron_variant	Intron 4 of 21	ENST00000260731.5	NP_004514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF11	ENST00000260731.5	c.387+236A>G		intron_variant	Intron 4 of 21	1	NM_004523.4	ENSP00000260731.3

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106212 AN: 151930 Hom.: 38494 Cov.: 31

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.667

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.699 AC: 106326 AN: 152048 Hom.: 38549 Cov.: 31 AF XY: 0.697 AC XY: 51812 AN XY: 74298

African (AFR) AF: 0.877 AC: 36434 AN: 41524

American (AMR) AF: 0.668 AC: 10186 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2348 AN: 3470

East Asian (EAS) AF: 0.926 AC: 4782 AN: 5166

South Asian (SAS) AF: 0.766 AC: 3696 AN: 4826

European-Finnish (FIN) AF: 0.582 AC: 6124 AN: 10526

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40485 AN: 67966

Other (OTH) AF: 0.667 AC: 1408 AN: 2112

Alfa AF: 0.665 Hom.: 10198

Bravo AF: 0.714

Asia WGS AF: 0.806 AC: 2801 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.32
DANN	Benign	0.59
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10786050; hg19: chr10-94367230;