rs4482220

Variant names:

• chr15-48809634-G-A
• rs4482220
• NM_001194998.2:c.-8+1327C>T

Variant summary

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

The NM_001194998.2(CEP152):​c.-8+1327C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,118 control chromosomes in the GnomAD database, including 4,013 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 0.21 (4013 hom., cov: 32)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.-8+1327C>T		intron_variant	Intron 1 of 26	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.-8+1327C>T		intron_variant	Intron 1 of 26	1	NM_001194998.2	ENSP00000370337.2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32072 AN: 152000 Hom.: 4012 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0822

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.192

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.211 AC: 32093 AN: 152118 Hom.: 4013 Cov.: 32 AF XY: 0.214 AC XY: 15893 AN XY: 74376

African (AFR) AF: 0.101 AC: 4202 AN: 41528

American (AMR) AF: 0.176 AC: 2689 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 731 AN: 3462

East Asian (EAS) AF: 0.0822 AC: 426 AN: 5184

South Asian (SAS) AF: 0.209 AC: 1005 AN: 4816

European-Finnish (FIN) AF: 0.362 AC: 3821 AN: 10560

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18429 AN: 67972

Other (OTH) AF: 0.190 AC: 401 AN: 2114

Alfa AF: 0.240 Hom.: 5689

Bravo AF: 0.189

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		-0.050
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: rs4482220; hg19: chr15-49101831;