rs16961470

Variant names:

• chr15-48724827-G-A
• rs16961470
• ENST00000561245.1:n.143-7658C>T

Variant summary

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

The ENST00000561245.1(CEP152):​n.143-7658C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,076 control chromosomes in the GnomAD database, including 1,996 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 0.15 (1996 hom., cov: 32)
• Consequence: CEP152 ENST00000561245.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 4 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000561245.1	n.143-7658C>T		intron_variant	Intron 2 of 3	2		ENSP00000453591.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23194 AN: 151958 Hom.: 1990 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.153 AC: 23197 AN: 152076 Hom.: 1996 Cov.: 32 AF XY: 0.154 AC XY: 11483 AN XY: 74330

African (AFR) AF: 0.183 AC: 7585 AN: 41482

American (AMR) AF: 0.124 AC: 1892 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3468

East Asian (EAS) AF: 0.383 AC: 1986 AN: 5186

South Asian (SAS) AF: 0.136 AC: 654 AN: 4814

European-Finnish (FIN) AF: 0.144 AC: 1521 AN: 10542

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8813 AN: 68000

Other (OTH) AF: 0.135 AC: 284 AN: 2110

Alfa AF: 0.135 Hom.: 177

Bravo AF: 0.157

Asia WGS AF: 0.219 AC: 761 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.9
DANN	Benign	0.77
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs16961470; hg19: chr15-49017024;