ENST00000676647.1:c.-131+919A>T

Variant names:

• chr10-92592748-A-T
• rs11187083
• ENST00000676647.1:c.-131+919A>T

Variant summary

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

The ENST00000676647.1(KIF11):​c.-131+919A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 151,946 control chromosomes in the GnomAD database, including 3,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (3610 hom., cov: 33)
• Consequence: KIF11 ENST00000676647.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.34
• Publications: 3 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=-0.77).
• BP6: Variant 10-92592748-A-T is Benign according to our data. Variant chr10-92592748-A-T is described in ClinVar as Benign. ClinVar VariationId is 1256778.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF11	ENST00000676647.1		c.-131+919A>T		intron	N/A	ENSP00000503394.1
	KIF11	ENST00000676757.1		c.-130-13517A>T		intron	N/A	ENSP00000504289.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22669 AN: 151828 Hom.: 3604 Cov.: 33

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.0945

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.00775

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0410

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.149 AC: 22710 AN: 151946 Hom.: 3610 Cov.: 33 AF XY: 0.144 AC XY: 10728 AN XY: 74282

African (AFR) AF: 0.399 AC: 16505 AN: 41378

American (AMR) AF: 0.122 AC: 1865 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3466

East Asian (EAS) AF: 0.0945 AC: 488 AN: 5162

South Asian (SAS) AF: 0.0776 AC: 374 AN: 4818

European-Finnish (FIN) AF: 0.00775 AC: 82 AN: 10576

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0410 AC: 2784 AN: 67952

Other (OTH) AF: 0.134 AC: 282 AN: 2108

Alfa AF: 0.0929 Hom.: 245

Bravo AF: 0.166

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.1
DANN	Benign	0.71
PhyloP100		1.3
PromoterAI		-0.036	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11187083; hg19: chr10-94352505;