rs9302144

Variant names:

• chr15-48767476-C-T
• rs9302144
• NM_001194998.2:c.2019-13G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-48767476-C-T
• chr15-48767476-C-A
• chr15-48767476-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001194998.2(CEP152):​c.2019-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,613,916 control chromosomes in the GnomAD database, including 1,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (506 hom., cov: 32)
  • Exomes 𝑓: 0.012 (937 hom.)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.749
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 15-48767476-C-T is Benign according to our data. Variant chr15-48767476-C-T is described in ClinVar as Benign. ClinVar VariationId is 136721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	NM_001194998.2	MANE Select	c.2019-13G>A		intron	N/A	NP_001181927.1	O94986-4
	CEP152	NM_014985.4		c.2019-13G>A		intron	N/A	NP_055800.2	O94986-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	ENST00000380950.7	TSL:1 MANE Select	c.2019-13G>A		intron	N/A	ENSP00000370337.2	O94986-4
	CEP152	ENST00000399334.7	TSL:1	c.2019-13G>A		intron	N/A	ENSP00000382271.3	O94986-3
	CEP152	ENST00000325747.9	TSL:1	c.1740-13G>A		intron	N/A	ENSP00000321000.5	O94986-1

Frequencies

GnomAD3 genomes AF: 0.0516 AC: 7846 AN: 152078 Hom.: 504 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0528

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.0871

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.00188

Gnomad OTH AF: 0.0435

GnomAD2 exomes AF: 0.0331 AC: 8256 AN: 249490 AF XY: 0.0273

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.100

Gnomad ASJ exome AF: 0.00695

Gnomad EAS exome AF: 0.0869

Gnomad FIN exome AF: 0.00107

Gnomad NFE exome AF: 0.00194

Gnomad OTH exome AF: 0.0170

GnomAD4 exome AF: 0.0117 AC: 17092 AN: 1461720 Hom.: 937 Cov.: 33 AF XY: 0.0107 AC XY: 7802 AN XY: 727152

African (AFR) AF: 0.155 AC: 5186 AN: 33474

American (AMR) AF: 0.0968 AC: 4327 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00593 AC: 155 AN: 26132

East Asian (EAS) AF: 0.0963 AC: 3823 AN: 39692

South Asian (SAS) AF: 0.0121 AC: 1047 AN: 86256

European-Finnish (FIN) AF: 0.00135 AC: 72 AN: 53354

Middle Eastern (MID) AF: 0.00798 AC: 46 AN: 5766

European-Non Finnish (NFE) AF: 0.00117 AC: 1304 AN: 1111934

Other (OTH) AF: 0.0187 AC: 1132 AN: 60390

GnomAD4 genome AF: 0.0516 AC: 7854 AN: 152196 Hom.: 506 Cov.: 32 AF XY: 0.0497 AC XY: 3696 AN XY: 74412

African (AFR) AF: 0.151 AC: 6252 AN: 41486

American (AMR) AF: 0.0529 AC: 809 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.0869 AC: 450 AN: 5176

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4826

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10608

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.00188 AC: 128 AN: 68018

Other (OTH) AF: 0.0430 AC: 91 AN: 2114

Alfa AF: 0.0193 Hom.: 304

Bravo AF: 0.0626

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Microcephaly 9, primary, autosomal recessive (1)
-	-	1	Seckel syndrome 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.067
DANN	Benign	0.62
PhyloP100		-0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs9302144; hg19: chr15-49059673; COSMIC: COSV57862651; COSMIC: COSV57862651;