rs1699400

Variant names:

• chr15-48755295-A-G
• rs1699400
• NM_001194998.2:c.3345+608T>C

Variant summary

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

The NM_001194998.2(CEP152):​c.3345+608T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 152,168 control chromosomes in the GnomAD database, including 640 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 0.073 (640 hom., cov: 32)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.3345+608T>C		intron_variant	Intron 20 of 26	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.3345+608T>C		intron_variant	Intron 20 of 26	1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7	c.3345+608T>C		intron_variant	Intron 20 of 25	1		ENSP00000382271.3
CEP152	ENST00000325747.9	c.3066+608T>C		intron_variant	Intron 19 of 24	1		ENSP00000321000.5

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 11097 AN: 152050 Hom.: 632 Cov.: 32

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0425

Gnomad OTH AF: 0.0770

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

GnomAD4 genome AF: 0.0730 AC: 11112 AN: 152168 Hom.: 640 Cov.: 32 AF XY: 0.0762 AC XY: 5672 AN XY: 74394

African (AFR) AF: 0.0833 AC: 3458 AN: 41530

American (AMR) AF: 0.174 AC: 2662 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 174 AN: 3470

East Asian (EAS) AF: 0.154 AC: 796 AN: 5182

South Asian (SAS) AF: 0.171 AC: 825 AN: 4814

European-Finnish (FIN) AF: 0.0111 AC: 118 AN: 10584

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0425 AC: 2888 AN: 68000

Other (OTH) AF: 0.0824 AC: 173 AN: 2100

Alfa AF: 0.0605 Hom.: 178

Bravo AF: 0.0848

Asia WGS AF: 0.183 AC: 633 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.23
PhyloP100		-0.037
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1699400; hg19: chr15-49047492;