Genetic Variant CEP152:c.87+23_87+27delAAAAA (chr15-48805535-CTTTTT-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001194998.2(CEP152):c.87+23_87+27delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,239,628 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

CEP152
NM_001194998.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.192

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: Likely_benign. The variant received -4 ACMG points.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000235 (265/1128110) while in subpopulation MID AF = 0.0027 (11/4076). AF 95% confidence interval is 0.00151. There are 1 homozygotes in GnomAdExome4. There are 125 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2 link	c.87+23_87+27delAAAAA		intron_variant	Intron 2 of 26	ENST00000380950.7	NP_001181927.1	O94986-4Q3B7A2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7 link	c.87+23_87+27delAAAAA		intron_variant	Intron 2 of 26	1	NM_001194998.2	ENSP00000370337.2		O94986-4

Frequencies

GnomAD3 genomes

AF:

0.000233

AC:

AN:

111502

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000606

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000887

Gnomad ASJ

AF:

0.000452

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000434

Gnomad OTH

AF:

0.000683

GnomAD2 exomes

AF:

0.000469

AC:

AN:

98152

AF XY:

0.000391

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.000809

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000461

Gnomad OTH exome

AF:

0.00121

GnomAD4 exome

AF:

0.000235

AC:

265

AN:

1128110

Hom.:

AF XY:

0.000221

AC XY:

125

AN XY:

564842

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

25912

American (AMR)

AF:

0.000836

AC:

AN:

32304

Ashkenazi Jewish (ASJ)

AF:

0.000556

AC:

AN:

19796

East Asian (EAS)

AF:

0.0000326

AC:

AN:

30702

South Asian (SAS)

AF:

0.0000870

AC:

AN:

68990

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33242

Middle Eastern (MID)

AF:

0.00270

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.000208

AC:

180

AN:

866860

Other (OTH)

AF:

0.000519

AC:

AN:

46228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000233

AC:

AN:

111518

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

54136

show subpopulations

African (AFR)

AF:

0.0000605

AC:

AN:

33060

American (AMR)

AF:

0.0000886

AC:

AN:

11282

Ashkenazi Jewish (ASJ)

AF:

0.000452

AC:

AN:

2210

East Asian (EAS)

AF:

0.00

AC:

AN:

4192

South Asian (SAS)

AF:

0.00

AC:

AN:

3602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

210

European-Non Finnish (NFE)

AF:

0.000434

AC:

AN:

48356

Other (OTH)

AF:

0.000678

AC:

AN:

1476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000380

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.19

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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15-48805535-CTTTTTTTTT-CTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over