rs148768851

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015634.4(KIFBP):c.68A>G(p.Glu23Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00122 in 1,614,230 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00072 ( 13 hom. )

Consequence

KIFBP
NM_015634.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:7

Conservation

PhyloP100: 7.05

Publications

4 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=0.006440878).

BP6

Variant 10-68988900-A-G is Benign according to our data. Variant chr10-68988900-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 158698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00605 (922/152352) while in subpopulation AFR AF = 0.0212 (882/41590). AF 95% confidence interval is 0.02. There are 8 homozygotes in GnomAd4. There are 417 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFBP	NM_015634.4 link	c.68A>G	p.Glu23Gly	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.68A>G	p.Glu23Gly	missense_variant	Exon 1 of 7	1	NM_015634.4	ENSP00000354848.4

Frequencies

GnomAD3 genomes

AF:

0.00605

AC:

921

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00178

AC:

446

AN:

251208

AF XY:

0.00132

show subpopulations

Gnomad AFR exome

AF:

0.0235

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000968

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.000720

AC:

1052

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

469

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0234

AC:

782

AN:

33480

American (AMR)

AF:

0.00132

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000980

AC:

109

AN:

1112012

Other (OTH)

AF:

0.00154

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

144

215

287

359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00605

AC:

922

AN:

152352

Hom.:

Cov.:

AF XY:

0.00560

AC XY:

417

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0212

AC:

882

AN:

41590

American (AMR)

AF:

0.00150

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68040

Other (OTH)

AF:

0.00521

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

106

160

213

266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00248

Hom.:

Bravo

AF:

0.00705

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0213

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00213

AC:

259

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Goldberg-Shprintzen syndrome

Uncertain:1Benign:2

Jan 12, 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. -

Aug 12, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 16, 2019

Clinical Genetics, Erasmus University Medical Center

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

Dec 04, 2017

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. -

May 17, 2016

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KIFBP: BS1, BS2 -

KIFBP-related disorder

Benign:1

Dec 26, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.82

T;T;T

MetaRNN

Benign

0.0064

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.3

M;.;.

PhyloP100

7.1

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-4.1

D;.;.

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

D;.;.

Sift4G

Uncertain

0.0090

D;.;D

Polyphen

1.0

D;.;.

Vest4

0.38

MVP

0.68

MPC

1.4

ClinPred

0.019

GERP RS

5.7

PromoterAI

0.027

Neutral

(source)

Varity_R

0.69

gMVP

0.75

Mutation Taster

=80/20

polymorphism

(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