Genetic Variant NM_198525.3:c.3112-11_3112-10insCT (chr15-89630503-C-CAG) – ACMG Classification: Benign (-16 pts)

Variant summary

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

The NM_198525.3(KIF7):c.3112-11_3112-10insCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,548,200 control chromosomes in the GnomAD database, including 253,302 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24302 hom., cov: 0)

Exomes 𝑓: 0.57 ( 229000 hom. )

Consequence

KIF7
NM_198525.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.261

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:

TICRR (HGNC:28704): (TOPBP1 interacting checkpoint and replication regulator) Enables chromatin binding activity. Involved in regulation of DNA-dependent DNA replication initiation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TICRR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 15-89630503-C-CAG is Benign according to our data. Variant chr15-89630503-C-CAG is described in ClinVar as [Benign]. Clinvar id is 263145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF7	NM_198525.3 link	c.3112-11_3112-10insCT		intron_variant	Intron 15 of 18	ENST00000394412.8	NP_940927.2	Q2M1P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF7	ENST00000394412.8 link	c.3112-11_3112-10insCT		intron_variant	Intron 15 of 18	5	NM_198525.3	ENSP00000377934.3		Q2M1P5

Frequencies

GnomAD3 genomes

AF:

0.563

AC:

85506

AN:

151820

Hom.:

24273

Cov.:

show subpopulations

Gnomad AFR

AF:

0.587

Gnomad AMI

AF:

0.610

Gnomad AMR

AF:

0.477

Gnomad ASJ

AF:

0.533

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.481

Gnomad FIN

AF:

0.612

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.585

Gnomad OTH

AF:

0.548

GnomAD3 exomes

AF:

0.527

AC:

81910

AN:

155468

Hom.:

22281

AF XY:

0.528

AC XY:

43273

AN XY:

82018

show subpopulations

Gnomad AFR exome

AF:

0.592

Gnomad AMR exome

AF:

0.432

Gnomad ASJ exome

AF:

0.533

Gnomad EAS exome

AF:

0.326

Gnomad SAS exome

AF:

0.498

Gnomad FIN exome

AF:

0.611

Gnomad NFE exome

AF:

0.585

Gnomad OTH exome

AF:

0.528

GnomAD4 exome

AF:

0.570

AC:

795399

AN:

1396262

Hom.:

229000

Cov.:

AF XY:

0.568

AC XY:

391080

AN XY:

688922

show subpopulations

Gnomad4 AFR exome

AF:

0.587

Gnomad4 AMR exome

AF:

0.438

Gnomad4 ASJ exome

AF:

0.538

Gnomad4 EAS exome

AF:

0.308

Gnomad4 SAS exome

AF:

0.504

Gnomad4 FIN exome

AF:

0.610

Gnomad4 NFE exome

AF:

0.588

Gnomad4 OTH exome

AF:

0.549

GnomAD4 genome

AF:

0.563

AC:

85580

AN:

151938

Hom.:

24302

Cov.:

AF XY:

0.559

AC XY:

41544

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.587

Gnomad4 AMR

AF:

0.478

Gnomad4 ASJ

AF:

0.533

Gnomad4 EAS

AF:

0.337

Gnomad4 SAS

AF:

0.480

Gnomad4 FIN

AF:

0.612

Gnomad4 NFE

AF:

0.585

Gnomad4 OTH

AF:

0.547

Alfa

AF:

0.500

Hom.:

2439

Bravo

AF:

0.553

Asia WGS

AF:

0.424

AC:

1476

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic 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

- -

Jul 02, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Acrocallosal syndrome

Benign:3

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hydrolethalus syndrome 2

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 01, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Multiple epiphyseal dysplasia, Al-Gazali type

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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