rs1426200

Variant names:

• chr15-48805819-C-A
• rs1426200
• NM_001194998.2:c.-7-163G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-48805819-C-A
• chr15-48805819-C-G
• chr15-48805819-C-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.-7-163G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,200 control chromosomes in the GnomAD database, including 56,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.86 (56092 hom., cov: 32)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.437
• 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=-0.89).
• BP6: Variant 15-48805819-C-A is Benign according to our data. Variant chr15-48805819-C-A is described in ClinVar as Benign. ClinVar VariationId is 678332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.-7-163G>T		intron	N/A	NP_001181927.1	O94986-4
	CEP152	NM_014985.4		c.-7-163G>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.-7-163G>T		intron	N/A	ENSP00000370337.2	O94986-4
	CEP152	ENST00000399334.7	TSL:1	c.-7-163G>T		intron	N/A	ENSP00000382271.3	O94986-3
	CEP152	ENST00000325747.9	TSL:1	c.-7-163G>T		intron	N/A	ENSP00000321000.5	O94986-1

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130196 AN: 152082 Hom.: 56042 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.869

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.856 AC: 130301 AN: 152200 Hom.: 56092 Cov.: 32 AF XY: 0.861 AC XY: 64075 AN XY: 74406

African (AFR) AF: 0.760 AC: 31552 AN: 41498

American (AMR) AF: 0.908 AC: 13897 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3178 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5177 AN: 5180

South Asian (SAS) AF: 0.931 AC: 4496 AN: 4830

European-Finnish (FIN) AF: 0.895 AC: 9483 AN: 10594

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59566 AN: 68010

Other (OTH) AF: 0.870 AC: 1836 AN: 2110

Alfa AF: 0.847 Hom.: 8034

Bravo AF: 0.853

Asia WGS AF: 0.957 AC: 3329 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.60
PhyloP100		0.44
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: rs1426200; hg19: chr15-49098016;