chr15-48740502-C-T

Variant names:

• chr15-48740502-C-T
• rs784405
• NM_001194998.2:c.4093+1099G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001194998.2(CEP152):​c.4093+1099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 151,980 control chromosomes in the GnomAD database, including 53,597 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.84 (53589 hom., cov: 30)
  • Exomes 𝑓: 0.68 (8 hom.)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.647
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

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.4093+1099G>A		intron	N/A	NP_001181927.1
	CEP152	NM_014985.4		c.3925+1099G>A		intron	N/A	NP_055800.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	ENST00000380950.7	TSL:1 MANE Select	c.4093+1099G>A		intron	N/A	ENSP00000370337.2
	CEP152	ENST00000399334.7	TSL:1	c.3925+1099G>A		intron	N/A	ENSP00000382271.3
	CEP152	ENST00000561245.1	TSL:2	n.142+1129G>A		intron	N/A	ENSP00000453591.1

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126852 AN: 151834 Hom.: 53531 Cov.: 30

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.679

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.794

GnomAD4 exome AF: 0.679 AC: 19 AN: 28 Hom.: 8 Cov.: 0 AF XY: 0.857 AC XY: 12 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.654 AC: 17 AN: 26

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.836 AC: 126969 AN: 151952 Hom.: 53589 Cov.: 30 AF XY: 0.841 AC XY: 62501 AN XY: 74282

African (AFR) AF: 0.939 AC: 38963 AN: 41514

American (AMR) AF: 0.824 AC: 12577 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2610 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5182 AN: 5190

South Asian (SAS) AF: 0.881 AC: 4246 AN: 4822

European-Finnish (FIN) AF: 0.862 AC: 9002 AN: 10448

Middle Eastern (MID) AF: 0.672 AC: 195 AN: 290

European-Non Finnish (NFE) AF: 0.762 AC: 51787 AN: 67928

Other (OTH) AF: 0.797 AC: 1684 AN: 2112

Alfa AF: 0.774 Hom.: 49416

Bravo AF: 0.838

Asia WGS AF: 0.933 AC: 3239 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.50
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs784405; hg19: chr15-49032699;