rs200879436

Positions:

chr15-48768237-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000380950.7(CEP152):c.2000A>G(p.Lys667Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000794 in 1,608,464 control chromosomes in the GnomAD database, including 14 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 9 hom. )

Consequence

CEP152
ENST00000380950.7 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: 3.58

Variant links:

Genes affected

CEP152 (HGNC:29298): (centrosomal protein 152) This gene encodes a protein that is thought to be involved with centrosome function. Mutations in this gene have been associated with primary microcephaly (MCPH4). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

CEP152 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=0.007913679).

BP6

Variant 15-48768237-T-C is Benign according to our data. Variant chr15-48768237-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 31034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48768237-T-C is described in Lovd as [Benign]. Variant chr15-48768237-T-C is described in Lovd as [Pathogenic].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00413 (629/152314) while in subpopulation AFR AF= 0.0145 (603/41560). AF 95% confidence interval is 0.0136. There are 5 homozygotes in gnomad4. There are 290 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP152	NM_001194998.2 linkuse as main transcript	c.2000A>G	p.Lys667Arg	missense_variant	15/27	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7 linkuse as main transcript	c.2000A>G	p.Lys667Arg	missense_variant	15/27	1	NM_001194998.2	ENSP00000370337	A2	O94986-4
CEP152	ENST00000399334.7 linkuse as main transcript	c.2000A>G	p.Lys667Arg	missense_variant	15/26	1		ENSP00000382271	P2	O94986-3
CEP152	ENST00000325747.9 linkuse as main transcript	c.1721A>G	p.Lys574Arg	missense_variant	14/25	1		ENSP00000321000	A2	O94986-1

Frequencies

GnomAD3 genomes

AF:

0.00411

AC:

625

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00102

AC:

254

AN:

249022

Hom.:

AF XY:

0.000844

AC XY:

114

AN XY:

135128

show subpopulations

Gnomad AFR exome

AF:

0.0151

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000445

AC:

648

AN:

1456150

Hom.:

Cov.:

AF XY:

0.000396

AC XY:

287

AN XY:

724864

show subpopulations

Gnomad4 AFR exome

AF:

0.0165

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000723

Gnomad4 OTH exome

AF:

0.000980

GnomAD4 genome

AF:

0.00413

AC:

629

AN:

152314

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

290

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0145

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000801

Hom.:

Bravo

AF:

0.00489

ESP6500AA

AF:

0.0129

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00113

AC:

137

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 14, 2019	This variant is associated with the following publications: (PMID: 21131973, 26206375, 25533962) -

Seckel syndrome 5

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2011

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 14, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.70

T;T;T

MetaRNN

Benign

0.0079

T;T;T

MetaSVM

Benign

-0.29

MutationAssessor

Uncertain

2.8

M;M;.

MutationTaster

Benign

0.93

D;D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.20

Sift

Uncertain

0.028

D;D;D

Sift4G

Benign

0.080

T;T;T

Polyphen

1.0

D;.;B

Vest4

0.35

MVP

0.76

MPC

0.36

ClinPred

0.040

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.51

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