15-48780830-C-A

Variant names:

• chr15-48780830-C-A
• rs16961635
• NM_001194998.2:c.1577+366G>T

Variant summary

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

The NM_001194998.2(CEP152):​c.1577+366G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,048 control chromosomes in the GnomAD database, including 5,335 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 0.23 (5335 hom., cov: 32)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 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.1577+366G>T		intron	N/A	NP_001181927.1
	CEP152	NM_014985.4		c.1577+366G>T		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.1577+366G>T		intron	N/A	ENSP00000370337.2
	CEP152	ENST00000399334.7	TSL:1	c.1577+366G>T		intron	N/A	ENSP00000382271.3
	CEP152	ENST00000325747.9	TSL:1	c.1298+366G>T		intron	N/A	ENSP00000321000.5

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34378 AN: 151930 Hom.: 5319 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0820

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.226 AC: 34420 AN: 152048 Hom.: 5335 Cov.: 32 AF XY: 0.226 AC XY: 16805 AN XY: 74326

African (AFR) AF: 0.424 AC: 17545 AN: 41424

American (AMR) AF: 0.182 AC: 2782 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0820 AC: 284 AN: 3464

East Asian (EAS) AF: 0.472 AC: 2439 AN: 5164

South Asian (SAS) AF: 0.152 AC: 734 AN: 4826

European-Finnish (FIN) AF: 0.142 AC: 1501 AN: 10580

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8527 AN: 67990

Other (OTH) AF: 0.191 AC: 403 AN: 2106

Alfa AF: 0.127 Hom.: 361

Bravo AF: 0.245

Asia WGS AF: 0.290 AC: 1007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.011
DANN	Benign	0.41
PhyloP100		-2.9
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: rs16961635; hg19: chr15-49073027;