15-89633201-T-G

Position:

chr15-89633201-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_198525.3(KIF7):c.2658A>C(p.Ala886=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 1,603,078 control chromosomes in the GnomAD database, including 641,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55566 hom., cov: 32)

Exomes 𝑓: 0.90 ( 585595 hom. )

Consequence

KIF7
NM_198525.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -1.05

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 15-89633201-T-G is Benign according to our data. Variant chr15-89633201-T-G is described in ClinVar as [Benign]. Clinvar id is 129413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-89633201-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.912 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.2658A>C	p.Ala886=	synonymous_variant	13/19	ENST00000394412.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
KIF7	ENST00000394412.8 linkuse as main transcript	c.2658A>C	p.Ala886=	synonymous_variant	13/19	5	NM_198525.3	P2
KIF7	ENST00000696512.1 linkuse as main transcript	c.2781A>C	p.Ala927=	synonymous_variant	13/19			A2
KIF7	ENST00000677187.1 linkuse as main transcript	n.332A>C		non_coding_transcript_exon_variant	1/7

Frequencies

GnomAD3 genomes

AF:

0.852

AC:

129491

AN:

152040

Hom.:

55528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.782

Gnomad AMI

AF:

0.949

Gnomad AMR

AF:

0.771

Gnomad ASJ

AF:

0.836

Gnomad EAS

AF:

0.701

Gnomad SAS

AF:

0.849

Gnomad FIN

AF:

0.888

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.918

Gnomad OTH

AF:

0.856

GnomAD3 exomes

AF:

0.849

AC:

200975

AN:

236596

Hom.:

86224

AF XY:

0.858

AC XY:

110159

AN XY:

128382

show subpopulations

Gnomad AFR exome

AF:

0.779

Gnomad AMR exome

AF:

0.714

Gnomad ASJ exome

AF:

0.843

Gnomad EAS exome

AF:

0.701

Gnomad SAS exome

AF:

0.865

Gnomad FIN exome

AF:

0.882

Gnomad NFE exome

AF:

0.916

Gnomad OTH exome

AF:

0.868

GnomAD4 exome

AF:

0.896

AC:

1300671

AN:

1450920

Hom.:

585595

Cov.:

AF XY:

0.897

AC XY:

647197

AN XY:

721534

show subpopulations

Gnomad4 AFR exome

AF:

0.776

Gnomad4 AMR exome

AF:

0.723

Gnomad4 ASJ exome

AF:

0.848

Gnomad4 EAS exome

AF:

0.669

Gnomad4 SAS exome

AF:

0.873

Gnomad4 FIN exome

AF:

0.886

Gnomad4 NFE exome

AF:

0.919

Gnomad4 OTH exome

AF:

0.883

GnomAD4 genome

AF:

0.852

AC:

129582

AN:

152158

Hom.:

55566

Cov.:

AF XY:

0.848

AC XY:

63081

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.782

Gnomad4 AMR

AF:

0.771

Gnomad4 ASJ

AF:

0.836

Gnomad4 EAS

AF:

0.701

Gnomad4 SAS

AF:

0.848

Gnomad4 FIN

AF:

0.888

Gnomad4 NFE

AF:

0.918

Gnomad4 OTH

AF:

0.852

Alfa

AF:

0.889

Hom.:

22034

Bravo

AF:

0.836

Asia WGS

AF:

0.772

AC:

2687

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 22, 2014	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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 DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

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	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

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

-0.92

CADD

Benign

0.25

DANN

Benign

0.42

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