rs150910683

Variant names:

• chr15-48738468-T-C
• rs150910683
• NM_001194998.2:c.4914A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001194998.2(CEP152):​c.4914A>G​(p.Pro1638Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000791 in 1,614,240 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (4 hom.)
• Consequence: CEP152 NM_001194998.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.09
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-48738468-T-C is Benign according to our data. Variant chr15-48738468-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 158269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.09 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00446 (679/152362) while in subpopulation AFR AF = 0.0156 (649/41586). AF 95% confidence interval is 0.0146. There are 1 homozygotes in GnomAd4. There are 328 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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.4914A>G	p.Pro1638Pro	synonymous	Exon 27 of 27	NP_001181927.1	O94986-4
	CEP152	NM_014985.4		c.4746A>G	p.Pro1582Pro	synonymous	Exon 26 of 26	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.4914A>G	p.Pro1638Pro	synonymous	Exon 27 of 27	ENSP00000370337.2	O94986-4
	CEP152	ENST00000399334.7	TSL:1	c.4746A>G	p.Pro1582Pro	synonymous	Exon 26 of 26	ENSP00000382271.3	O94986-3
	CEP152	ENST00000561245.1	TSL:2	n.142+3163A>G		intron	N/A	ENSP00000453591.1	H0YMG1

Frequencies

GnomAD3 genomes AF: 0.00441 AC: 671 AN: 152244 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000978 AC: 244 AN: 249430 AF XY: 0.000702

Gnomad AFR exome AF: 0.0141

Gnomad AMR exome AF: 0.000666

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.000409 AC: 598 AN: 1461878 Hom.: 4 Cov.: 31 AF XY: 0.000364 AC XY: 265 AN XY: 727240

African (AFR) AF: 0.0149 AC: 499 AN: 33480

American (AMR) AF: 0.000850 AC: 38 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1111998

Other (OTH) AF: 0.000828 AC: 50 AN: 60396

GnomAD4 genome AF: 0.00446 AC: 679 AN: 152362 Hom.: 1 Cov.: 32 AF XY: 0.00440 AC XY: 328 AN XY: 74508

African (AFR) AF: 0.0156 AC: 649 AN: 41586

American (AMR) AF: 0.00163 AC: 25 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00309 Hom.: 5

Bravo AF: 0.00490

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.46
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

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: rs150910683; hg19: chr15-49030665;