chr10-92592178-C-T

Variant names:

• chr10-92592178-C-T
• rs11595187
• ENST00000676647.1:c.-131+349C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000676647.1(KIF11):​c.-131+349C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.091 in 152,070 control chromosomes in the GnomAD database, including 755 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.091 (755 hom., cov: 32)
• Consequence: KIF11 ENST00000676647.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000676647.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF11	ENST00000676647.1		c.-131+349C>T		intron	N/A	ENSP00000503394.1
	KIF11	ENST00000676757.1		c.-130-14087C>T		intron	N/A	ENSP00000504289.1

Frequencies

GnomAD3 genomes AF: 0.0910 AC: 13822 AN: 151952 Hom.: 754 Cov.: 32

Gnomad AFR AF: 0.0919

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0498

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0534

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.0790

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

GnomAD4 genome AF: 0.0910 AC: 13843 AN: 152070 Hom.: 755 Cov.: 32 AF XY: 0.0922 AC XY: 6852 AN XY: 74328

African (AFR) AF: 0.0917 AC: 3807 AN: 41494

American (AMR) AF: 0.148 AC: 2267 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0498 AC: 173 AN: 3472

East Asian (EAS) AF: 0.126 AC: 649 AN: 5136

South Asian (SAS) AF: 0.165 AC: 794 AN: 4824

European-Finnish (FIN) AF: 0.0534 AC: 565 AN: 10588

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0793 AC: 5390 AN: 67952

Other (OTH) AF: 0.0810 AC: 171 AN: 2110

Alfa AF: 0.0896 Hom.: 84

Bravo AF: 0.0974

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.67
PhyloP100		-0.74
PromoterAI		0.0059	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11595187; hg19: chr10-94351935;