ENST00000676757.1:c.-131+828A>C

Variant names:

• chr10-92575021-A-C
• rs3758505
• ENST00000676757.1:c.-131+828A>C

Variant summary

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

The ENST00000676757.1(KIF11):​c.-131+828A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,124 control chromosomes in the GnomAD database, including 2,830 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 0.16 (2830 hom., cov: 32)
• Consequence: KIF11 ENST00000676757.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000676757.1. 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	ENST00000676757.1		c.-131+828A>C		intron	N/A	ENSP00000504289.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24427 AN: 152006 Hom.: 2818 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0544

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0880

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.161 AC: 24480 AN: 152124 Hom.: 2830 Cov.: 32 AF XY: 0.159 AC XY: 11843 AN XY: 74366

African (AFR) AF: 0.319 AC: 13209 AN: 41468

American (AMR) AF: 0.177 AC: 2707 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 195 AN: 3472

East Asian (EAS) AF: 0.127 AC: 658 AN: 5176

South Asian (SAS) AF: 0.169 AC: 817 AN: 4824

European-Finnish (FIN) AF: 0.0544 AC: 577 AN: 10606

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0880 AC: 5988 AN: 68012

Other (OTH) AF: 0.142 AC: 300 AN: 2106

Alfa AF: 0.199 Hom.: 1122

Bravo AF: 0.176

Asia WGS AF: 0.149 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.48
PhyloP100		-0.30

Splicing

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

Other links and lift over

dbSNP: rs3758505; hg19: chr10-94334778;