rs75503597

Variant names:

• chr15-48797937-C-T
• rs75503597
• NM_001194998.2:c.191+11G>A

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.191+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 1,608,296 control chromosomes in the GnomAD database, including 1,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (112 hom., cov: 32)
  • Exomes 𝑓: 0.028 (905 hom.)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.50
• Publications: 2 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=-0.88).
• BP6: Variant 15-48797937-C-T is Benign according to our data. Variant chr15-48797937-C-T is described in ClinVar as Benign. ClinVar VariationId is 158236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0741 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.191+11G>A		intron	N/A	NP_001181927.1	O94986-4
	CEP152	NM_014985.4		c.191+11G>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.191+11G>A		intron	N/A	ENSP00000370337.2	O94986-4
	CEP152	ENST00000399334.7	TSL:1	c.191+11G>A		intron	N/A	ENSP00000382271.3	O94986-3
	CEP152	ENST00000325747.9	TSL:1	c.191+11G>A		intron	N/A	ENSP00000321000.5	O94986-1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3840 AN: 152112 Hom.: 112 Cov.: 32

Gnomad AFR AF: 0.00463

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.0805

Gnomad SAS AF: 0.0335

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0250

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.0350 AC: 8697 AN: 248324 AF XY: 0.0355

Gnomad AFR exome AF: 0.00421

Gnomad AMR exome AF: 0.00673

Gnomad ASJ exome AF: 0.0135

Gnomad EAS exome AF: 0.0883

Gnomad FIN exome AF: 0.102

Gnomad NFE exome AF: 0.0296

Gnomad OTH exome AF: 0.0262

GnomAD4 exome AF: 0.0284 AC: 41372 AN: 1456066 Hom.: 905 Cov.: 30 AF XY: 0.0287 AC XY: 20820 AN XY: 724674

African (AFR) AF: 0.00294 AC: 98 AN: 33330

American (AMR) AF: 0.00760 AC: 339 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.0145 AC: 379 AN: 26102

East Asian (EAS) AF: 0.0791 AC: 3138 AN: 39666

South Asian (SAS) AF: 0.0344 AC: 2958 AN: 86000

European-Finnish (FIN) AF: 0.0970 AC: 5175 AN: 53352

Middle Eastern (MID) AF: 0.0210 AC: 121 AN: 5752

European-Non Finnish (NFE) AF: 0.0247 AC: 27382 AN: 1107092

Other (OTH) AF: 0.0296 AC: 1782 AN: 60182

GnomAD4 genome AF: 0.0252 AC: 3838 AN: 152230 Hom.: 112 Cov.: 32 AF XY: 0.0291 AC XY: 2165 AN XY: 74410

African (AFR) AF: 0.00462 AC: 192 AN: 41548

American (AMR) AF: 0.00980 AC: 150 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3468

East Asian (EAS) AF: 0.0805 AC: 417 AN: 5182

South Asian (SAS) AF: 0.0335 AC: 162 AN: 4830

European-Finnish (FIN) AF: 0.105 AC: 1112 AN: 10568

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0251 AC: 1704 AN: 68016

Other (OTH) AF: 0.0199 AC: 42 AN: 2112

Alfa AF: 0.0215 Hom.: 21

Bravo AF: 0.0179

Asia WGS AF: 0.0510 AC: 175 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	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	-0.88
CADD	Benign	0.54
DANN	Benign	0.46
PhyloP100		-1.5
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: rs75503597; hg19: chr15-49090134;