rs17107764

Variant names:

• chr10-92632702-A-T
• rs17107764
• NM_004523.4:c.1702+9A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004523.4(KIF11):​c.1702+9A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 1,562,260 control chromosomes in the GnomAD database, including 8,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (3604 hom., cov: 32)
  • Exomes 𝑓: 0.054 (4542 hom.)
• Consequence: KIF11 NM_004523.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.745
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-92632702-A-T is Benign according to our data. Variant chr10-92632702-A-T is described in ClinVar as Benign. ClinVar VariationId is 259408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004523.4. 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
	KIF11	NM_004523.4	MANE Select	c.1702+9A>T		intron	N/A	NP_004514.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF11	ENST00000260731.5	TSL:1 MANE Select	c.1702+9A>T		intron	N/A	ENSP00000260731.3
	KIF11	ENST00000676647.1		c.1495+9A>T		intron	N/A	ENSP00000503394.1
	KIF11	ENST00000676757.1		c.1495+9A>T		intron	N/A	ENSP00000504289.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22672 AN: 151916 Hom.: 3598 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.0949

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.00775

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0409

Gnomad OTH AF: 0.135

GnomAD2 exomes AF: 0.0804 AC: 18194 AN: 226312 AF XY: 0.0736

Gnomad AFR exome AF: 0.410

Gnomad AMR exome AF: 0.0972

Gnomad ASJ exome AF: 0.0484

Gnomad EAS exome AF: 0.115

Gnomad FIN exome AF: 0.00886

Gnomad NFE exome AF: 0.0411

Gnomad OTH exome AF: 0.0631

GnomAD4 exome AF: 0.0540 AC: 76140 AN: 1410226 Hom.: 4542 Cov.: 24 AF XY: 0.0533 AC XY: 37401 AN XY: 701202

African (AFR) AF: 0.413 AC: 13024 AN: 31502

American (AMR) AF: 0.0946 AC: 3740 AN: 39554

Ashkenazi Jewish (ASJ) AF: 0.0491 AC: 1193 AN: 24288

East Asian (EAS) AF: 0.0895 AC: 3519 AN: 39308

South Asian (SAS) AF: 0.0697 AC: 5632 AN: 80762

European-Finnish (FIN) AF: 0.0111 AC: 582 AN: 52628

Middle Eastern (MID) AF: 0.0926 AC: 513 AN: 5538

European-Non Finnish (NFE) AF: 0.0407 AC: 43926 AN: 1078266

Other (OTH) AF: 0.0687 AC: 4011 AN: 58380

GnomAD4 genome AF: 0.149 AC: 22713 AN: 152034 Hom.: 3604 Cov.: 32 AF XY: 0.144 AC XY: 10736 AN XY: 74320

African (AFR) AF: 0.398 AC: 16510 AN: 41436

American (AMR) AF: 0.122 AC: 1864 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3470

East Asian (EAS) AF: 0.0950 AC: 489 AN: 5150

South Asian (SAS) AF: 0.0774 AC: 373 AN: 4818

European-Finnish (FIN) AF: 0.00775 AC: 82 AN: 10580

Middle Eastern (MID) AF: 0.117 AC: 34 AN: 290

European-Non Finnish (NFE) AF: 0.0409 AC: 2785 AN: 68024

Other (OTH) AF: 0.134 AC: 281 AN: 2104

Alfa AF: 0.0793 Hom.: 279

Bravo AF: 0.166

Asia WGS AF: 0.108 AC: 377 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.0
DANN	Benign	0.70
PhyloP100		0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs17107764; hg19: chr10-94392459; COSMIC: COSV53270980;