rs58156069

Variant names:

• chr15-48791380-C-T
• rs58156069
• NM_001194998.2:c.833-4G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-48791380-C-T
• chr15-48791380-C-A
• chr15-48791380-C-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.833-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,607,084 control chromosomes in the GnomAD database, including 157,597 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12474 hom., cov: 31)
  • Exomes 𝑓: 0.44 (145123 hom.)
• Consequence: CEP152 NM_001194998.2 splice_region, intron
• Scores: Splicing: ADA: 0.00002314
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.136
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-48791380-C-T is Benign according to our data. Variant chr15-48791380-C-T is described in ClinVar as Benign. ClinVar VariationId is 158274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 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.833-4G>A		splice_region intron	N/A	NP_001181927.1	O94986-4
	CEP152	NM_014985.4		c.833-4G>A		splice_region 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.833-4G>A		splice_region intron	N/A	ENSP00000370337.2	O94986-4
	CEP152	ENST00000399334.7	TSL:1	c.833-4G>A		splice_region intron	N/A	ENSP00000382271.3	O94986-3
	CEP152	ENST00000325747.9	TSL:1	c.554-4G>A		splice_region intron	N/A	ENSP00000321000.5	O94986-1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60237 AN: 151566 Hom.: 12474 Cov.: 31

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.444

GnomAD2 exomes AF: 0.399 AC: 98822 AN: 247492 AF XY: 0.408

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.321

Gnomad ASJ exome AF: 0.502

Gnomad EAS exome AF: 0.346

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.451

Gnomad OTH exome AF: 0.433

GnomAD4 exome AF: 0.442 AC: 643661 AN: 1455398 Hom.: 145123 Cov.: 33 AF XY: 0.442 AC XY: 319984 AN XY: 724310

African (AFR) AF: 0.300 AC: 10037 AN: 33402

American (AMR) AF: 0.330 AC: 14753 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 12809 AN: 26086

East Asian (EAS) AF: 0.333 AC: 13178 AN: 39590

South Asian (SAS) AF: 0.397 AC: 34158 AN: 86088

European-Finnish (FIN) AF: 0.327 AC: 16681 AN: 51066

Middle Eastern (MID) AF: 0.478 AC: 2747 AN: 5750

European-Non Finnish (NFE) AF: 0.463 AC: 512849 AN: 1108524

Other (OTH) AF: 0.439 AC: 26449 AN: 60210

GnomAD4 genome AF: 0.397 AC: 60248 AN: 151686 Hom.: 12474 Cov.: 31 AF XY: 0.390 AC XY: 28909 AN XY: 74100

African (AFR) AF: 0.310 AC: 12796 AN: 41322

American (AMR) AF: 0.406 AC: 6198 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1751 AN: 3470

East Asian (EAS) AF: 0.335 AC: 1727 AN: 5158

South Asian (SAS) AF: 0.370 AC: 1767 AN: 4780

European-Finnish (FIN) AF: 0.322 AC: 3382 AN: 10488

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.457 AC: 31062 AN: 67900

Other (OTH) AF: 0.439 AC: 928 AN: 2112

Alfa AF: 0.449 Hom.: 6272

Bravo AF: 0.402

Asia WGS AF: 0.289 AC: 1007 AN: 3476

EpiCase AF: 0.472

EpiControl AF: 0.487

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	not provided (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	-0.82
CADD	Benign	9.4
DANN	Benign	0.44
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.012
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: rs58156069; hg19: chr15-49083577; COSMIC: COSV57857885; COSMIC: COSV57857885;