NM_004523.4:c.698+322G>T

Variant names:

• chr10-92609831-G-T
• rs11187096
• NM_004523.4:c.698+322G>T

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.698+322G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,998 control chromosomes in the GnomAD database, including 8,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (8230 hom., cov: 31)
• Consequence: KIF11 NM_004523.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.305
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 10-92609831-G-T is Benign according to our data. Variant chr10-92609831-G-T is described in ClinVar as Benign. ClinVar VariationId is 1296598.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF11	NM_004523.4	c.698+322G>T		intron_variant	Intron 6 of 21	ENST00000260731.5	NP_004514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF11	ENST00000260731.5	c.698+322G>T		intron_variant	Intron 6 of 21	1	NM_004523.4	ENSP00000260731.3

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47032 AN: 151880 Hom.: 8228 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.310 AC: 47051 AN: 151998 Hom.: 8230 Cov.: 31 AF XY: 0.314 AC XY: 23336 AN XY: 74296

African (AFR) AF: 0.173 AC: 7162 AN: 41480

American (AMR) AF: 0.261 AC: 3982 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3470

East Asian (EAS) AF: 0.672 AC: 3469 AN: 5160

South Asian (SAS) AF: 0.469 AC: 2259 AN: 4818

European-Finnish (FIN) AF: 0.392 AC: 4136 AN: 10548

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.347 AC: 23596 AN: 67956

Other (OTH) AF: 0.321 AC: 675 AN: 2106

Alfa AF: 0.195 Hom.: 438

Bravo AF: 0.297

Asia WGS AF: 0.507 AC: 1759 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 17, 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	1.2
DANN	Benign	0.73
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11187096; hg19: chr10-94369588;