rs2255607

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_015634.4(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. 14/21 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
NM_015634.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.335

Publications

36 publications found

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 Gene-Disease associations (from GenCC):

Goldberg-Shprintzen syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

KIFBP 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 (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 VariationId is 158696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
KIFBP	NM_015634.4 link	c.196G>A	p.Gly66Ser	missense_variant	Exon 1 of 7	ENST00000361983.7	NP_056449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFBP	ENST00000361983.7 link	c.196G>A	p.Gly66Ser	missense_variant	Exon 1 of 7	1	NM_015634.4	ENSP00000354848.4		Q96EK5

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

GnomAD2 exomes

AF:

0.404

AC:

100114

AN:

247738

AF XY:

0.406

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 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

African (AFR)

AF:

0.346

AC:

11578

AN:

33472

American (AMR)

AF:

0.301

AC:

13461

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

9133

AN:

26112

East Asian (EAS)

AF:

0.355

AC:

14089

AN:

39690

South Asian (SAS)

AF:

0.318

AC:

27445

AN:

86240

European-Finnish (FIN)

AF:

0.403

AC:

21511

AN:

53312

Middle Eastern (MID)

AF:

0.416

AC:

2398

AN:

5764

European-Non Finnish (NFE)

AF:

0.492

AC:

547160

AN:

1111824

Other (OTH)

AF:

0.438

AC:

26416

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

23990

47980

71969

95959

119949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15812

31624

47436

63248

79060

<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:

0.414

AC:

63053

AN:

152210

Hom.:

13505

Cov.:

AF XY:

0.407

AC XY:

30306

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.347

AC:

14424

AN:

41558

American (AMR)

AF:

0.350

AC:

5353

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.361

AC:

1255

AN:

3472

East Asian (EAS)

AF:

0.366

AC:

1889

AN:

5158

South Asian (SAS)

AF:

0.310

AC:

1499

AN:

4828

European-Finnish (FIN)

AF:

0.394

AC:

4173

AN:

10592

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.486

AC:

33017

AN:

67982

Other (OTH)

AF:

0.430

AC:

910

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1925

3850

5775

7700

9625

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

588

1176

1764

2352

2940

<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:

0.430

Hom.:

11281

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Sep 21, 2015

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

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 11, 2016

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. -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

May 07, 2018

Athena Diagnostics

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

- -

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

(source)

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;.;.

PhyloP100

0.34

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

PromoterAI

-0.071

Neutral

(source)

Varity_R

0.037

gMVP

0.12

Mutation Taster

=100/0

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