rs9672296

Positions:

chr15-89631724-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198525.3(KIF7):c.2896-14G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,542,734 control chromosomes in the GnomAD database, including 246,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21740 hom., cov: 33)

Exomes 𝑓: 0.56 ( 224362 hom. )

Consequence

KIF7
NM_198525.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.908

Variant links:

Genes affected

KIF7 (HGNC:30497): (kinesin family member 7) This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies. [provided by RefSeq, Oct 2011]

KIF7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-89631724-C-T is Benign according to our data. Variant chr15-89631724-C-T is described in ClinVar as [Benign]. Clinvar id is 96652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-89631724-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF7	NM_198525.3 linkuse as main transcript	c.2896-14G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000394412.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
KIF7	ENST00000394412.8 linkuse as main transcript	c.2896-14G>A	splice_polypyrimidine_tract_variant, intron_variant	5	NM_198525.3	P2
KIF7	ENST00000696512.1 linkuse as main transcript	c.3019-14G>A	splice_polypyrimidine_tract_variant, intron_variant			A2
KIF7	ENST00000677187.1 linkuse as main transcript	n.570-14G>A	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80743

AN:

151958

Hom.:

21721

Cov.:

show subpopulations

Gnomad AFR

AF:

0.483

Gnomad AMI

AF:

0.610

Gnomad AMR

AF:

0.457

Gnomad ASJ

AF:

0.537

Gnomad EAS

AF:

0.333

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.613

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.513

GnomAD3 exomes

AF:

0.513

AC:

76741

AN:

149570

Hom.:

20469

AF XY:

0.516

AC XY:

41073

AN XY:

79554

show subpopulations

Gnomad AFR exome

AF:

0.482

Gnomad AMR exome

AF:

0.418

Gnomad ASJ exome

AF:

0.531

Gnomad EAS exome

AF:

0.318

Gnomad SAS exome

AF:

0.490

Gnomad FIN exome

AF:

0.609

Gnomad NFE exome

AF:

0.578

Gnomad OTH exome

AF:

0.511

GnomAD4 exome

AF:

0.564

AC:

784976

AN:

1390656

Hom.:

224362

Cov.:

AF XY:

0.563

AC XY:

385357

AN XY:

684902

show subpopulations

Gnomad4 AFR exome

AF:

0.478

Gnomad4 AMR exome

AF:

0.422

Gnomad4 ASJ exome

AF:

0.541

Gnomad4 EAS exome

AF:

0.305

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.610

Gnomad4 NFE exome

AF:

0.586

Gnomad4 OTH exome

AF:

0.537

GnomAD4 genome

AF:

0.531

AC:

80802

AN:

152078

Hom.:

21740

Cov.:

AF XY:

0.529

AC XY:

39348

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.483

Gnomad4 AMR

AF:

0.457

Gnomad4 ASJ

AF:

0.537

Gnomad4 EAS

AF:

0.335

Gnomad4 SAS

AF:

0.478

Gnomad4 FIN

AF:

0.613

Gnomad4 NFE

AF:

0.583

Gnomad4 OTH

AF:

0.512

Alfa

AF:

0.566

Hom.:

37935

Bravo

AF:

0.516

Asia WGS

AF:

0.416

AC:

1449

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 14, 2014	- -

Acrocallosal syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Hydrolethalus syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Multiple epiphyseal dysplasia, Al-Gazali type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.1

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over