15-48738079-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001194998.2(CEP152):c.*170T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0344 in 748,566 control chromosomes in the GnomAD database, including 539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (117 hom., cov: 32)
  • Exomes 𝑓: 0.034 (422 hom.)
• Consequence: CEP152 NM_001194998.2 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.90

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 15-48738079-A-G is Benign according to our data. Variant chr15-48738079-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 316405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0349 (5324/152346) while in subpopulation AFR AF= 0.043 (1786/41576). AF 95% confidence interval is 0.0413. There are 117 homozygotes in gnomad4. There are 2502 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 117 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP152	NM_001194998.2	c.*170T>C		3_prime_UTR_variant	27/27	ENST00000380950.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP152	ENST00000380950.7	c.*170T>C		3_prime_UTR_variant	27/27	1	NM_001194998.2	A2
CEP152	ENST00000561245.1	c.142+3552T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0350 AC: 5329 AN: 152228 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0317

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0223

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.0383

GnomAD4 exome AF: 0.0343 AC: 20423 AN: 596220 Hom.: 422 Cov.: 8 AF XY: 0.0340 AC XY: 10445 AN XY: 307158

Gnomad4 AFR exome AF: 0.0428

Gnomad4 AMR exome AF: 0.0280

Gnomad4 ASJ exome AF: 0.0413

Gnomad4 EAS exome AF: 0.0000643

Gnomad4 SAS exome AF: 0.0245

Gnomad4 FIN exome AF: 0.0140

Gnomad4 NFE exome AF: 0.0388

Gnomad4 OTH exome AF: 0.0353

GnomAD4 genome AF: 0.0349 AC: 5324 AN: 152346 Hom.: 117 Cov.: 32 AF XY: 0.0336 AC XY: 2502 AN XY: 74496

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.0316

Gnomad4 ASJ AF: 0.0409

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0222

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.0381

Gnomad4 OTH AF: 0.0379

Alfa AF: 0.0353 Hom.: 34

Bravo AF: 0.0368

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Microcephaly 9, primary, autosomal recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Seckel syndrome 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	16
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2169757; hg19: chr15-49030276;