rs784416

Variant names:

• chr15-48720728-G-C
• rs784416
• ENST00000561245.1:n.143-3559C>G

Variant summary

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

The ENST00000561245.1(CEP152):​n.143-3559C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 152,220 control chromosomes in the GnomAD database, including 71,998 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 0.97 (71998 hom., cov: 30)
• Consequence: CEP152 ENST00000561245.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.989 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.143-3559C>G		intron_variant	Intron 2 of 3	2		ENSP00000453591.1

Frequencies

GnomAD3 genomes AF: 0.971 AC: 147660 AN: 152100 Hom.: 71947 Cov.: 30

Gnomad AFR AF: 0.991

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.964

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

GnomAD4 genome AF: 0.971 AC: 147761 AN: 152220 Hom.: 71998 Cov.: 30 AF XY: 0.966 AC XY: 71893 AN XY: 74426

African (AFR) AF: 0.991 AC: 41165 AN: 41520

American (AMR) AF: 0.859 AC: 13118 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.991 AC: 3440 AN: 3472

East Asian (EAS) AF: 0.846 AC: 4366 AN: 5162

South Asian (SAS) AF: 0.852 AC: 4101 AN: 4816

European-Finnish (FIN) AF: 0.999 AC: 10610 AN: 10618

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67730 AN: 68036

Other (OTH) AF: 0.958 AC: 2025 AN: 2114

Alfa AF: 0.985 Hom.: 8116

Bravo AF: 0.962

Asia WGS AF: 0.827 AC: 2880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.58
PhyloP100		0.025

Splicing

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

Other links and lift over

dbSNP: rs784416; hg19: chr15-49012925;