NM_001194998.2:c.691+9C>T

Variant names:

• chr15-48796001-G-A
• rs77732888
• NM_001194998.2:c.691+9C>T

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.691+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 1,611,154 control chromosomes in the GnomAD database, including 6,593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (472 hom., cov: 32)
  • Exomes 𝑓: 0.087 (6121 hom.)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.00900
• Publications: 4 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=-0.67).
• BP6: Variant 15-48796001-G-A is Benign according to our data. Variant chr15-48796001-G-A is described in ClinVar as Benign. ClinVar VariationId is 136720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0974 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.691+9C>T		intron	N/A	NP_001181927.1	O94986-4
	CEP152	NM_014985.4		c.691+9C>T		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.691+9C>T		intron	N/A	ENSP00000370337.2	O94986-4
	CEP152	ENST00000399334.7	TSL:1	c.691+9C>T		intron	N/A	ENSP00000382271.3	O94986-3
	CEP152	ENST00000325747.9	TSL:1	c.412+9C>T		intron	N/A	ENSP00000321000.5	O94986-1

Frequencies

GnomAD3 genomes AF: 0.0707 AC: 10751 AN: 152034 Hom.: 472 Cov.: 32

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0847

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0294

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.0903

GnomAD2 exomes AF: 0.0713 AC: 17755 AN: 249162 AF XY: 0.0739

Gnomad AFR exome AF: 0.0337

Gnomad AMR exome AF: 0.0585

Gnomad ASJ exome AF: 0.0970

Gnomad EAS exome AF: 0.000557

Gnomad FIN exome AF: 0.0362

Gnomad NFE exome AF: 0.0983

Gnomad OTH exome AF: 0.0913

GnomAD4 exome AF: 0.0870 AC: 126885 AN: 1459002 Hom.: 6121 Cov.: 31 AF XY: 0.0867 AC XY: 62976 AN XY: 725954

African (AFR) AF: 0.0317 AC: 1059 AN: 33440

American (AMR) AF: 0.0628 AC: 2805 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2675 AN: 26100

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39656

South Asian (SAS) AF: 0.0619 AC: 5331 AN: 86184

European-Finnish (FIN) AF: 0.0394 AC: 2099 AN: 53300

Middle Eastern (MID) AF: 0.147 AC: 848 AN: 5756

European-Non Finnish (NFE) AF: 0.0962 AC: 106776 AN: 1109566

Other (OTH) AF: 0.0876 AC: 5284 AN: 60300

GnomAD4 genome AF: 0.0707 AC: 10753 AN: 152152 Hom.: 472 Cov.: 32 AF XY: 0.0676 AC XY: 5026 AN XY: 74382

African (AFR) AF: 0.0342 AC: 1419 AN: 41504

American (AMR) AF: 0.0846 AC: 1292 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0528 AC: 255 AN: 4828

European-Finnish (FIN) AF: 0.0294 AC: 311 AN: 10588

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0994 AC: 6760 AN: 67990

Other (OTH) AF: 0.0888 AC: 188 AN: 2116

Alfa AF: 0.0800 Hom.: 356

Bravo AF: 0.0711

Asia WGS AF: 0.0240 AC: 83 AN: 3478

EpiCase AF: 0.107

EpiControl AF: 0.105

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	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	-0.67
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		0.0090
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs77732888; hg19: chr15-49088198; COSMIC: COSV57866607; COSMIC: COSV57866607;