15-48747600-T-C

Variant names:

• chr15-48747600-T-C
• rs784411
• NM_001194998.2:c.3634+843A>G

Variant summary

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

The NM_001194998.2(CEP152):​c.3634+843A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,058 control chromosomes in the GnomAD database, including 10,711 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 0.32 (10711 hom., cov: 32)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942
• Publications: 13 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 = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.3634+843A>G		intron_variant	Intron 22 of 26	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.3634+843A>G		intron_variant	Intron 22 of 26	1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7	c.3467-2608A>G		intron_variant	Intron 21 of 25	1		ENSP00000382271.3
CEP152	ENST00000325747.9	c.3355+843A>G		intron_variant	Intron 21 of 24	1		ENSP00000321000.5

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48793 AN: 151940 Hom.: 10677 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.321 AC: 48865 AN: 152058 Hom.: 10711 Cov.: 32 AF XY: 0.324 AC XY: 24085 AN XY: 74358

African (AFR) AF: 0.581 AC: 24084 AN: 41466

American (AMR) AF: 0.363 AC: 5553 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3466

East Asian (EAS) AF: 0.629 AC: 3248 AN: 5164

South Asian (SAS) AF: 0.326 AC: 1572 AN: 4824

European-Finnish (FIN) AF: 0.153 AC: 1619 AN: 10584

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11502 AN: 67962

Other (OTH) AF: 0.287 AC: 604 AN: 2108

Alfa AF: 0.223 Hom.: 16405

Bravo AF: 0.354

Asia WGS AF: 0.482 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.43
PhyloP100		-0.94
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: rs784411; hg19: chr15-49039797;