rs7174453

Variant names:

• chr15-48725156-A-G
• rs7174453
• ENST00000561245.1:n.143-7987T>C

Variant summary

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

The ENST00000561245.1(CEP152):​n.143-7987T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 152,218 control chromosomes in the GnomAD database, including 391 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 0.046 (391 hom., cov: 32)
• Consequence: CEP152 ENST00000561245.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76
• 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

ENSG00000259216 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 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.143-7987T>C		intron_variant	Intron 2 of 3	2		ENSP00000453591.1
ENSG00000259216	ENST00000559987.2	n.-182A>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 7044 AN: 152100 Hom.: 389 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.0881

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00185

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0463 AC: 7054 AN: 152218 Hom.: 391 Cov.: 32 AF XY: 0.0449 AC XY: 3338 AN XY: 74424

African (AFR) AF: 0.132 AC: 5476 AN: 41504

American (AMR) AF: 0.0516 AC: 788 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3468

East Asian (EAS) AF: 0.0880 AC: 456 AN: 5184

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4820

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00185 AC: 126 AN: 68022

Other (OTH) AF: 0.0398 AC: 84 AN: 2110

Alfa AF: 0.0212 Hom.: 58

Bravo AF: 0.0563

Asia WGS AF: 0.0570 AC: 198 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0080
DANN	Benign	0.47
PhyloP100		-2.8

Splicing

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

Other links and lift over

dbSNP: rs7174453; hg19: chr15-49017353;