rs72750755

Positions:

chr15-89645161-A-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_198525.3(KIF7):c.2043T>A(p.Val681Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,604,452 control chromosomes in the GnomAD database, including 1,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 86 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1361 hom. )

Consequence

KIF7
NM_198525.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.294

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 -16 ACMG points.

BP6

Variant 15-89645161-A-T is Benign according to our data. Variant chr15-89645161-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 129409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-89645161-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF7	NM_198525.3 linkuse as main transcript	c.2043T>A	p.Val681Val	synonymous_variant	10/19	ENST00000394412.8	NP_940927.2	Q2M1P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF7	ENST00000394412.8 linkuse as main transcript	c.2043T>A	p.Val681Val	synonymous_variant	10/19	5	NM_198525.3	ENSP00000377934.3		Q2M1P5
KIF7	ENST00000696512.1 linkuse as main transcript	c.2166T>A	p.Val722Val	synonymous_variant	10/19			ENSP00000512678.1		A0A8Q3SIQ8

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4466

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00700

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0296

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0566

Gnomad FIN

AF:

0.0269

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0434

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0350

AC:

8516

AN:

243136

Hom.:

215

AF XY:

0.0381

AC XY:

5040

AN XY:

132402

show subpopulations

Gnomad AFR exome

AF:

0.00609

Gnomad AMR exome

AF:

0.0184

Gnomad ASJ exome

AF:

0.0294

Gnomad EAS exome

AF:

0.000273

Gnomad SAS exome

AF:

0.0622

Gnomad FIN exome

AF:

0.0363

Gnomad NFE exome

AF:

0.0427

Gnomad OTH exome

AF:

0.0370

GnomAD4 exome

AF:

0.0399

AC:

57934

AN:

1452158

Hom.:

1361

Cov.:

AF XY:

0.0409

AC XY:

29576

AN XY:

722876

show subpopulations

Gnomad4 AFR exome

AF:

0.00624

Gnomad4 AMR exome

AF:

0.0191

Gnomad4 ASJ exome

AF:

0.0304

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0635

Gnomad4 FIN exome

AF:

0.0398

Gnomad4 NFE exome

AF:

0.0417

Gnomad4 OTH exome

AF:

0.0359

GnomAD4 genome

AF:

0.0293

AC:

4467

AN:

152294

Hom.:

Cov.:

AF XY:

0.0292

AC XY:

2172

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00698

Gnomad4 AMR

AF:

0.0295

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0570

Gnomad4 FIN

AF:

0.0269

Gnomad4 NFE

AF:

0.0434

Gnomad4 OTH

AF:

0.0407

Alfa

AF:

0.0382

Hom.:

Bravo

AF:

0.0269

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.0462

EpiControl

AF:

0.0429

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

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, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 21, 2014	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. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Acrocallosal syndrome

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.40

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.40

Position offset: -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