rs16961671

Variant names:

• chr15-48807718-C-T
• rs16961671
• NM_001194998.2:c.-7-2062G>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.-7-2062G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 152,252 control chromosomes in the GnomAD database, including 274 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 0.029 (274 hom., cov: 33)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.689
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.-7-2062G>A		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.-7-2062G>A		intron_variant	Intron 1 of 26	1	NM_001194998.2	ENSP00000370337.2

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 4472 AN: 152132 Hom.: 270 Cov.: 33

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0234

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.00670

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00513

Gnomad OTH AF: 0.0341

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

GnomAD4 genome AF: 0.0295 AC: 4486 AN: 152252 Hom.: 274 Cov.: 33 AF XY: 0.0342 AC XY: 2548 AN XY: 74434

African (AFR) AF: 0.0129 AC: 537 AN: 41560

American (AMR) AF: 0.124 AC: 1900 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0234 AC: 81 AN: 3468

East Asian (EAS) AF: 0.154 AC: 796 AN: 5170

South Asian (SAS) AF: 0.138 AC: 666 AN: 4826

European-Finnish (FIN) AF: 0.00670 AC: 71 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00513 AC: 349 AN: 68024

Other (OTH) AF: 0.0408 AC: 86 AN: 2106

Alfa AF: 0.0156 Hom.: 13

Bravo AF: 0.0354

Asia WGS AF: 0.174 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.8
DANN	Benign	0.72
PhyloP100		0.69
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: rs16961671; hg19: chr15-49099915;