15-48738304-G-A

Variant names:

Variant summary

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

The NM_001194998.2(CEP152):c.5078C>T(p.Pro1693Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,613,914 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1693S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00097 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 40 hom. )

Consequence

CEP152
NM_001194998.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.945

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

microcephaly with or without short stature
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Seckel syndrome 5
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
microcephaly 9, primary, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal recessive primary microcephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Seckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP152 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=0.004120499).

BP6

Variant 15-48738304-G-A is Benign according to our data. Variant chr15-48738304-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 158270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000972 (148/152186) while in subpopulation SAS AF = 0.0278 (134/4828). AF 95% confidence interval is 0.0239. There are 2 homozygotes in GnomAd4. There are 109 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001194998.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	NM_001194998.2	MANE Select	c.5078C>T	p.Pro1693Leu	missense	Exon 27 of 27	NP_001181927.1	O94986-4
	CEP152	NM_014985.4		c.4910C>T	p.Pro1637Leu	missense	Exon 26 of 26	NP_055800.2	O94986-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEP152	ENST00000380950.7	TSL:1 MANE Select	c.5078C>T	p.Pro1693Leu	missense	Exon 27 of 27	ENSP00000370337.2	O94986-4
CEP152	ENST00000399334.7	TSL:1	c.4910C>T	p.Pro1637Leu	missense	Exon 26 of 26	ENSP00000382271.3	O94986-3
CEP152	ENST00000561245.1	TSL:2	n.142+3327C>T		intron	N/A	ENSP00000453591.1	H0YMG1

Frequencies

GnomAD3 genomes

AF:

0.000980

AC:

149

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0279

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.00319

AC:

794

AN:

249196

AF XY:

0.00432

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00149

AC:

2176

AN:

1461728

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

1576

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39688

South Asian (SAS)

AF:

0.0237

AC:

2046

AN:

86248

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000243

AC:

AN:

1111894

Other (OTH)

AF:

0.00151

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

133

266

400

533

666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.000972

AC:

148

AN:

152186

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

109

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41534

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.0278

AC:

134

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68016

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

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:

0.000121

Hom.:

Bravo

AF:

0.000196

ExAC

AF:

0.00367

AC:

444

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Microcephaly 9, primary, autosomal recessive (1)

Seckel syndrome 5 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0082

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

0.94

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.035

Sift

Benign

0.059

Sift4G

Benign

0.23

Vest4

0.21

MVP

0.28

MPC

0.10

ClinPred

0.0095

GERP RS

2.7

Varity_R

0.046

gMVP

0.027

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over