Variant 15-89646817-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198525.3(KIF7):c.1788+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,612,020 control chromosomes in the GnomAD database, including 294,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26907 hom., cov: 31)

Exomes 𝑓: 0.60 ( 267683 hom. )

Consequence

KIF7
NM_198525.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -2.76

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 15-89646817-A-G is Benign according to our data. Variant chr15-89646817-A-G is described in ClinVar as [Benign]. Clinvar id is 263138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-89646817-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF7	NM_198525.3 link	c.1788+13T>C		intron_variant		ENST00000394412.8	NP_940927.2	Q2M1P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF7	ENST00000394412.8 link	c.1788+13T>C		intron_variant		5	NM_198525.3	ENSP00000377934.3		Q2M1P5
KIF7	ENST00000696512.1 link	c.1911+13T>C		intron_variant				ENSP00000512678.1		A0A8Q3SIQ8

Frequencies

GnomAD3 genomes

AF:

0.592

AC:

89796

AN:

151668

Hom.:

26878

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.632

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.480

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.619

Gnomad OTH

AF:

0.564

GnomAD3 exomes

AF:

0.560

AC:

140214

AN:

250600

Hom.:

40482

AF XY:

0.562

AC XY:

76172

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.623

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.562

Gnomad EAS exome

AF:

0.357

Gnomad SAS exome

AF:

0.498

Gnomad FIN exome

AF:

0.625

Gnomad NFE exome

AF:

0.623

Gnomad OTH exome

AF:

0.571

GnomAD4 exome

AF:

0.602

AC:

878687

AN:

1460234

Hom.:

267683

Cov.:

AF XY:

0.599

AC XY:

435368

AN XY:

726522

show subpopulations

Gnomad4 AFR exome

AF:

0.619

Gnomad4 AMR exome

AF:

0.447

Gnomad4 ASJ exome

AF:

0.563

Gnomad4 EAS exome

AF:

0.340

Gnomad4 SAS exome

AF:

0.502

Gnomad4 FIN exome

AF:

0.627

Gnomad4 NFE exome

AF:

0.625

Gnomad4 OTH exome

AF:

0.586

GnomAD4 genome

AF:

0.592

AC:

89870

AN:

151786

Hom.:

26907

Cov.:

AF XY:

0.589

AC XY:

43705

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.616

Gnomad4 AMR

AF:

0.505

Gnomad4 ASJ

AF:

0.551

Gnomad4 EAS

AF:

0.368

Gnomad4 SAS

AF:

0.479

Gnomad4 FIN

AF:

0.629

Gnomad4 NFE

AF:

0.619

Gnomad4 OTH

AF:

0.561

Alfa

AF:

0.602

Hom.:

35313

Bravo

AF:

0.584

Asia WGS

AF:

0.437

AC:

1521

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 12, 2016	- -
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	Genome-Nilou Lab	Aug 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Hydrolethalus syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

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

-0.79

CADD

Benign

0.017

DANN

Benign

0.72

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