rs2255607

Positions:

Variant summary

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

The ENST00000361983.7(KIFBP):c.196G>A(p.Gly66Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,613,698 control chromosomes in the GnomAD database, including 172,227 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13505 hom., cov: 34)

Exomes 𝑓: 0.46 ( 158722 hom. )

Consequence

KIFBP
ENST00000361983.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.335

Variant links:

Genes affected

KIFBP (HGNC:23419): (kinesin family binding protein) This gene encodes a kinesin family member 1 binding protein that is characterized by two tetratrico peptide repeats. The encoded protein localizes to the mitochondria and may be involved in regulating transport of the mitochondria. Mutations in this gene are associated with Goldberg-Shprintzen megacolon syndrome. [provided by RefSeq, Mar 2010]

KIFBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6480684E-4).

BP6

Variant 10-68989028-G-A is Benign according to our data. Variant chr10-68989028-G-A is described in ClinVar as [Benign]. Clinvar id is 158696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-68989028-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIFBP	NM_015634.4 linkuse as main transcript	c.196G>A	p.Gly66Ser	missense_variant	1/7	ENST00000361983.7	NP_056449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIFBP	ENST00000361983.7 linkuse as main transcript	c.196G>A	p.Gly66Ser	missense_variant	1/7	1	NM_015634.4	ENSP00000354848	P1

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

63049

AN:

152092

Hom.:

13502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.442

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.361

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.486

Gnomad OTH

AF:

0.434

GnomAD3 exomes

AF:

0.404

AC:

100114

AN:

247738

Hom.:

21164

AF XY:

0.406

AC XY:

54687

AN XY:

134566

show subpopulations

Gnomad AFR exome

AF:

0.350

Gnomad AMR exome

AF:

0.293

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.372

Gnomad SAS exome

AF:

0.313

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.484

Gnomad OTH exome

AF:

0.401

GnomAD4 exome

AF:

0.461

AC:

673191

AN:

1461488

Hom.:

158722

Cov.:

AF XY:

0.456

AC XY:

331844

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.346

Gnomad4 AMR exome

AF:

0.301

Gnomad4 ASJ exome

AF:

0.350

Gnomad4 EAS exome

AF:

0.355

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.403

Gnomad4 NFE exome

AF:

0.492

Gnomad4 OTH exome

AF:

0.438

GnomAD4 genome

AF:

0.414

AC:

63053

AN:

152210

Hom.:

13505

Cov.:

AF XY:

0.407

AC XY:

30306

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.347

Gnomad4 AMR

AF:

0.350

Gnomad4 ASJ

AF:

0.361

Gnomad4 EAS

AF:

0.366

Gnomad4 SAS

AF:

0.310

Gnomad4 FIN

AF:

0.394

Gnomad4 NFE

AF:

0.486

Gnomad4 OTH

AF:

0.430

Alfa

AF:

0.429

Hom.:

7720

Bravo

AF:

0.411

TwinsUK

AF:

0.491

AC:

1819

ALSPAC

AF:

0.506

AC:

1952

ESP6500AA

AF:

0.342

AC:

1507

ESP6500EA

AF:

0.483

AC:

4153

ExAC

AF:

0.410

AC:

49681

Asia WGS

AF:

0.304

AC:

1058

AN:

3478

EpiCase

AF:

0.476

EpiControl

AF:

0.474

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Goldberg-Shprintzen syndrome

Benign:4

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 11, 2016	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, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.2

DANN

Benign

0.84

DEOGEN2

Benign

0.019

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.69

T;T;T

MetaRNN

Benign

0.00016

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.5

L;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.030

N;.;.

REVEL

Benign

0.011

Sift

Benign

0.55

T;.;.

Sift4G

Benign

0.37

T;.;T

Polyphen

0.0

B;.;.

Vest4

0.043

MPC

0.45

ClinPred

0.00074

GERP RS

-0.11

Varity_R

0.037

gMVP

0.12

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