chr15-89652935-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000445906.1(KIF7):n.-5T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 1,507,096 control chromosomes in the GnomAD database, including 2,058 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 149 hom., cov: 33)

Exomes 𝑓: 0.051 ( 1909 hom. )

Consequence

KIF7
ENST00000445906.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.362

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

acrocallosal syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
hydrolethalus syndrome 2
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
hydrolethalus syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
multiple epiphyseal dysplasia, Al-Gazali type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
orofaciodigital syndrome type 6
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

KIF7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-89652935-A-C is Benign according to our data. Variant chr15-89652935-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF7	NM_198525.3 link	c.-5T>G		5_prime_UTR_variant	Exon 2 of 19	ENST00000394412.8	NP_940927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
KIF7	ENST00000445906.1 link	n.-5T>G		non_coding_transcript_exon_variant	Exon 2 of 5	1		ENSP00000395906.1
KIF7	ENST00000394412.8 link	c.-5T>G		5_prime_UTR_variant	Exon 2 of 19	5	NM_198525.3	ENSP00000377934.3
KIF7	ENST00000445906.1 link	n.-5T>G		5_prime_UTR_variant	Exon 2 of 5	1		ENSP00000395906.1
KIF7	ENST00000696512.1 link	c.119T>G	p.Leu40Arg	missense_variant	Exon 2 of 19			ENSP00000512678.1

Frequencies

GnomAD3 genomes

AF:

0.0402

AC:

6117

AN:

152146

Hom.:

148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0135

Gnomad AMI

AF:

0.0582

Gnomad AMR

AF:

0.0377

Gnomad ASJ

AF:

0.0507

Gnomad EAS

AF:

0.0946

Gnomad SAS

AF:

0.0334

Gnomad FIN

AF:

0.0325

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0538

Gnomad OTH

AF:

0.0397

GnomAD2 exomes

AF:

0.0483

AC:

5738

AN:

118826

AF XY:

0.0476

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.0339

Gnomad ASJ exome

AF:

0.0600

Gnomad EAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.0420

Gnomad NFE exome

AF:

0.0541

Gnomad OTH exome

AF:

0.0450

GnomAD4 exome

AF:

0.0509

AC:

68952

AN:

1354832

Hom.:

1909

Cov.:

AF XY:

0.0506

AC XY:

33574

AN XY:

663094

show subpopulations

African (AFR)

AF:

0.0112

AC:

348

AN:

31014

American (AMR)

AF:

0.0363

AC:

1249

AN:

34368

Ashkenazi Jewish (ASJ)

AF:

0.0588

AC:

1371

AN:

23310

East Asian (EAS)

AF:

0.0878

AC:

3089

AN:

35202

South Asian (SAS)

AF:

0.0334

AC:

2504

AN:

74882

European-Finnish (FIN)

AF:

0.0443

AC:

1692

AN:

38214

Middle Eastern (MID)

AF:

0.0516

AC:

243

AN:

4708

European-Non Finnish (NFE)

AF:

0.0529

AC:

55906

AN:

1056876

Other (OTH)

AF:

0.0453

AC:

2550

AN:

56258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

3006

6011

9017

12022

15028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2158

4316

6474

8632

10790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0402

AC:

6119

AN:

152264

Hom.:

149

Cov.:

AF XY:

0.0394

AC XY:

2935

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0135

AC:

560

AN:

41566

American (AMR)

AF:

0.0377

AC:

576

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0507

AC:

176

AN:

3470

East Asian (EAS)

AF:

0.0948

AC:

490

AN:

5168

South Asian (SAS)

AF:

0.0330

AC:

159

AN:

4820

European-Finnish (FIN)

AF:

0.0325

AC:

345

AN:

10616

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0538

AC:

3658

AN:

68008

Other (OTH)

AF:

0.0416

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

321

642

962

1283

1604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0481

Hom.:

Bravo

AF:

0.0397

Asia WGS

AF:

0.0440

AC:

152

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 30, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 07, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Acrocallosal syndrome

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

0.36

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over