chr15-48811047-T-C

Variant names:

• chr15-48811047-T-C
• rs2304546
• NM_001194998.2:c.-94A>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.-94A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,338 control chromosomes in the GnomAD database, including 1,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1547 hom., cov: 33)
  • Exomes 𝑓: 0.073 (1 hom.)
• Consequence: CEP152 NM_001194998.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.581
• Publications: 11 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

ENSG00000259700 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-48811047-T-C is Benign according to our data. Variant chr15-48811047-T-C is described in ClinVar as Benign. ClinVar VariationId is 316436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 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.-94A>G		5_prime_UTR	Exon 1 of 27	NP_001181927.1
	CEP152	NM_014985.4		c.-94A>G		5_prime_UTR	Exon 1 of 26	NP_055800.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	ENST00000380950.7	TSL:1 MANE Select	c.-94A>G		5_prime_UTR	Exon 1 of 27	ENSP00000370337.2
	CEP152	ENST00000560322.5	TSL:1	n.-94A>G		non_coding_transcript_exon	Exon 1 of 13	ENSP00000453440.1
	CEP152	ENST00000560322.5	TSL:1	n.-94A>G		5_prime_UTR	Exon 1 of 13	ENSP00000453440.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18914 AN: 152138 Hom.: 1535 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.0885

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0787

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.0732 AC: 6 AN: 82 Hom.: 1 Cov.: 0 AF XY: 0.0370 AC XY: 2 AN XY: 54

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0323 AC: 2 AN: 62

Other (OTH) AF: 0.200 AC: 2 AN: 10

GnomAD4 genome AF: 0.124 AC: 18954 AN: 152256 Hom.: 1547 Cov.: 33 AF XY: 0.131 AC XY: 9746 AN XY: 74454

African (AFR) AF: 0.144 AC: 5984 AN: 41552

American (AMR) AF: 0.235 AC: 3589 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 241 AN: 3472

East Asian (EAS) AF: 0.296 AC: 1523 AN: 5152

South Asian (SAS) AF: 0.208 AC: 1006 AN: 4828

European-Finnish (FIN) AF: 0.0885 AC: 940 AN: 10624

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0787 AC: 5351 AN: 68012

Other (OTH) AF: 0.130 AC: 275 AN: 2116

Alfa AF: 0.0981 Hom.: 1630

Bravo AF: 0.138

Asia WGS AF: 0.278 AC: 965 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	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	-0.85
CADD	Benign	4.2
DANN	Benign	0.70
PhyloP100		-0.58
PromoterAI		-0.096	Neutral
Mutation Taster		=204/96	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2304546; hg19: chr15-49103244; COSMIC: COSV57858881; COSMIC: COSV57858881;