chr15-48783032-T-G

Variant names:

• chr15-48783032-T-G
• rs16961645
• NM_001194998.2:c.1322-802A>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.1322-802A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,084 control chromosomes in the GnomAD database, including 1,889 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 0.15 (1889 hom., cov: 32)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• 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

ENSG00000259670 (HGNC:58297):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001194998.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	NM_001194998.2	MANE Select	c.1322-802A>C		intron	N/A	NP_001181927.1
	CEP152	NM_014985.4		c.1322-802A>C		intron	N/A	NP_055800.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	ENST00000380950.7	TSL:1 MANE Select	c.1322-802A>C		intron	N/A	ENSP00000370337.2
	CEP152	ENST00000399334.7	TSL:1	c.1322-802A>C		intron	N/A	ENSP00000382271.3
	CEP152	ENST00000325747.9	TSL:1	c.1043-802A>C		intron	N/A	ENSP00000321000.5

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22470 AN: 151966 Hom.: 1883 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.148 AC: 22471 AN: 152084 Hom.: 1889 Cov.: 32 AF XY: 0.150 AC XY: 11148 AN XY: 74344

African (AFR) AF: 0.177 AC: 7357 AN: 41490

American (AMR) AF: 0.121 AC: 1857 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0764 AC: 265 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1986 AN: 5148

South Asian (SAS) AF: 0.135 AC: 650 AN: 4824

European-Finnish (FIN) AF: 0.141 AC: 1490 AN: 10582

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8388 AN: 67974

Other (OTH) AF: 0.132 AC: 278 AN: 2106

Alfa AF: 0.144 Hom.: 625

Bravo AF: 0.153

Asia WGS AF: 0.220 AC: 764 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.19
DANN	Benign	0.55
PhyloP100		-1.3
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: rs16961645; hg19: chr15-49075229;