chr15-48781706-A-G

Variant names:

• chr15-48781706-A-G
• rs7176696
• NM_001194998.2:c.1414-347T>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.1414-347T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,030 control chromosomes in the GnomAD database, including 11,795 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 0.33 (11795 hom., cov: 32)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.1414-347T>C		intron_variant	Intron 11 of 26	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.1414-347T>C		intron_variant	Intron 11 of 26	1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7	c.1414-347T>C		intron_variant	Intron 11 of 25	1		ENSP00000382271.3
CEP152	ENST00000325747.9	c.1135-347T>C		intron_variant	Intron 10 of 24	1		ENSP00000321000.5
CEP152	ENST00000560322.5	n.1414-347T>C		intron_variant	Intron 11 of 12	1		ENSP00000453440.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50546 AN: 151912 Hom.: 11760 Cov.: 32

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.333 AC: 50619 AN: 152030 Hom.: 11795 Cov.: 32 AF XY: 0.335 AC XY: 24893 AN XY: 74320

African (AFR) AF: 0.623 AC: 25806 AN: 41422

American (AMR) AF: 0.367 AC: 5597 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3470

East Asian (EAS) AF: 0.627 AC: 3237 AN: 5164

South Asian (SAS) AF: 0.327 AC: 1573 AN: 4810

European-Finnish (FIN) AF: 0.154 AC: 1632 AN: 10586

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11480 AN: 67994

Other (OTH) AF: 0.291 AC: 613 AN: 2110

Alfa AF: 0.238 Hom.: 1322

Bravo AF: 0.368

Asia WGS AF: 0.481 AC: 1670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.27
DANN	Benign	0.48
PhyloP100		-1.4
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: rs7176696; hg19: chr15-49073903;