10-92576042-A-G

Variant names:

• chr10-92576042-A-G
• rs7099761
• ENST00000676757.1:c.-131+1849A>G

Variant summary

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

The ENST00000676757.1(KIF11):​c.-131+1849A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,956 control chromosomes in the GnomAD database, including 15,911 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 0.45 (15911 hom., cov: 31)
• Consequence: KIF11 ENST00000676757.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 4 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF11	ENST00000676757.1	c.-131+1849A>G		intron_variant	Intron 1 of 21			ENSP00000504289.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68623 AN: 151838 Hom.: 15901 Cov.: 31

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.452 AC: 68654 AN: 151956 Hom.: 15911 Cov.: 31 AF XY: 0.452 AC XY: 33585 AN XY: 74252

African (AFR) AF: 0.405 AC: 16788 AN: 41448

American (AMR) AF: 0.373 AC: 5690 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2107 AN: 3466

East Asian (EAS) AF: 0.721 AC: 3723 AN: 5162

South Asian (SAS) AF: 0.586 AC: 2819 AN: 4814

European-Finnish (FIN) AF: 0.441 AC: 4638 AN: 10522

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31231 AN: 67974

Other (OTH) AF: 0.466 AC: 985 AN: 2112

Alfa AF: 0.453 Hom.: 6724

Bravo AF: 0.446

Asia WGS AF: 0.600 AC: 2083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.3
DANN	Benign	0.78
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs7099761; hg19: chr10-94335799;