rs16961455

Variant names:

• chr15-48719626-C-T
• rs16961455
• ENST00000561245.1:n.143-2457G>A

Variant summary

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

The ENST00000561245.1(CEP152):​n.143-2457G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 152,142 control chromosomes in the GnomAD database, including 549 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 0.069 (549 hom., cov: 32)
• Consequence: CEP152 ENST00000561245.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000561245.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	ENST00000561245.1	TSL:2	n.143-2457G>A		intron	N/A	ENSP00000453591.1	H0YMG1

Frequencies

GnomAD3 genomes AF: 0.0693 AC: 10529 AN: 152024 Hom.: 548 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0588

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.0925

Gnomad FIN AF: 0.0928

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0860

Gnomad OTH AF: 0.0727

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

GnomAD4 genome AF: 0.0692 AC: 10523 AN: 152142 Hom.: 549 Cov.: 32 AF XY: 0.0712 AC XY: 5296 AN XY: 74378

African (AFR) AF: 0.0170 AC: 705 AN: 41502

American (AMR) AF: 0.0587 AC: 896 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0496 AC: 172 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1284 AN: 5170

South Asian (SAS) AF: 0.0919 AC: 443 AN: 4820

European-Finnish (FIN) AF: 0.0928 AC: 983 AN: 10598

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0860 AC: 5848 AN: 67994

Other (OTH) AF: 0.0720 AC: 152 AN: 2112

Alfa AF: 0.0644 Hom.: 215

Bravo AF: 0.0664

Asia WGS AF: 0.139 AC: 482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.65
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs16961455; hg19: chr15-49011823;