rs11631496

Variant names:

• chr15-48783721-T-C
• rs11631496
• NM_001194998.2:c.1321+252A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-48783721-T-C
• chr15-48783721-T-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001194998.2(CEP152):​c.1321+252A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 149,444 control chromosomes in the GnomAD database, including 2,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2563 hom., cov: 30)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.312
• Publications: 1 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

CEP152-AS1 (HGNC:58297):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-48783721-T-C is Benign according to our data. Variant chr15-48783721-T-C is described in ClinVar as Benign. ClinVar VariationId is 668868.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 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.1321+252A>G		intron	N/A	NP_001181927.1	O94986-4
	CEP152	NM_014985.4		c.1321+252A>G		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.1321+252A>G		intron	N/A	ENSP00000370337.2	O94986-4
	CEP152	ENST00000399334.7	TSL:1	c.1321+252A>G		intron	N/A	ENSP00000382271.3	O94986-3
	CEP152	ENST00000325747.9	TSL:1	c.1042+252A>G		intron	N/A	ENSP00000321000.5	O94986-1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 24626 AN: 149402 Hom.: 2563 Cov.: 30

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.165 AC: 24620 AN: 149444 Hom.: 2563 Cov.: 30 AF XY: 0.159 AC XY: 11610 AN XY: 72894

African (AFR) AF: 0.0609 AC: 2498 AN: 41010

American (AMR) AF: 0.177 AC: 2649 AN: 14932

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 856 AN: 3454

East Asian (EAS) AF: 0.00156 AC: 8 AN: 5144

South Asian (SAS) AF: 0.123 AC: 585 AN: 4772

European-Finnish (FIN) AF: 0.143 AC: 1351 AN: 9424

Middle Eastern (MID) AF: 0.337 AC: 95 AN: 282

European-Non Finnish (NFE) AF: 0.237 AC: 15970 AN: 67456

Other (OTH) AF: 0.203 AC: 418 AN: 2062

Alfa AF: 0.217 Hom.: 1999

Bravo AF: 0.161

Asia WGS AF: 0.0690 AC: 238 AN: 3444

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.65
PhyloP100		-0.31
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: rs11631496; hg19: chr15-49075918;