rs145377591

Variant names:

• chr15-48717160-G-T
• rs145377591
• ENST00000561245.1:n.152C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-48717160-G-T
• chr15-48717160-G-A
• chr15-48717160-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000561245.1(CEP152):​n.152C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0073 in 455,410 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (12 hom.)
• Consequence: CEP152 ENST00000561245.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0240
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-48717160-G-T is Benign according to our data. Variant chr15-48717160-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2645316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0068 (1032/151704) while in subpopulation NFE AF = 0.00937 (637/67988). AF 95% confidence interval is 0.00877. There are 8 homozygotes in GnomAd4. There are 497 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000561245.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	ENST00000561245.1	TSL:2	n.152C>A		non_coding_transcript_exon	Exon 3 of 4	ENSP00000453591.1	H0YMG1

Frequencies

GnomAD3 genomes AF: 0.00679 AC: 1030 AN: 151600 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00189

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.00887

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00562

Gnomad FIN AF: 0.00720

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.00937

Gnomad OTH AF: 0.0106

GnomAD2 exomes AF: 0.00631 AC: 807 AN: 127982 AF XY: 0.00629

Gnomad AFR exome AF: 0.00198

Gnomad AMR exome AF: 0.00707

Gnomad ASJ exome AF: 0.00247

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00613

Gnomad NFE exome AF: 0.00875

Gnomad OTH exome AF: 0.00827

GnomAD4 exome AF: 0.00754 AC: 2291 AN: 303706 Hom.: 12 Cov.: 0 AF XY: 0.00731 AC XY: 1264 AN XY: 172956

African (AFR) AF: 0.00232 AC: 20 AN: 8612

American (AMR) AF: 0.00697 AC: 190 AN: 27272

Ashkenazi Jewish (ASJ) AF: 0.00278 AC: 30 AN: 10784

East Asian (EAS) AF: 0.00 AC: 0 AN: 9204

South Asian (SAS) AF: 0.00551 AC: 329 AN: 59736

European-Finnish (FIN) AF: 0.00760 AC: 94 AN: 12364

Middle Eastern (MID) AF: 0.00978 AC: 27 AN: 2762

European-Non Finnish (NFE) AF: 0.00939 AC: 1490 AN: 158760

Other (OTH) AF: 0.00781 AC: 111 AN: 14212

GnomAD4 genome AF: 0.00680 AC: 1032 AN: 151704 Hom.: 8 Cov.: 32 AF XY: 0.00671 AC XY: 497 AN XY: 74086

African (AFR) AF: 0.00189 AC: 78 AN: 41326

American (AMR) AF: 0.00886 AC: 135 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00604 AC: 29 AN: 4800

European-Finnish (FIN) AF: 0.00720 AC: 75 AN: 10420

Middle Eastern (MID) AF: 0.0414 AC: 12 AN: 290

European-Non Finnish (NFE) AF: 0.00937 AC: 637 AN: 67988

Other (OTH) AF: 0.0105 AC: 22 AN: 2096

Alfa AF: 0.00564 Hom.: 2

Bravo AF: 0.00646

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.77
PhyloP100		-0.024

Splicing

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

Other links and lift over

dbSNP: rs145377591; hg19: chr15-49009357;