rs16967572

Variant names:

• chr19-32921607-G-C
• rs16967572
• NM_032816.5:c.1268+1832C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032816.5(CEP89):​c.1268+1832C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,180 control chromosomes in the GnomAD database, including 5,877 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5877 hom., cov: 33)
• Consequence: CEP89 NM_032816.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 7 publications found

Genes affected

CEP89 (HGNC:25907): (centrosomal protein 89) Involved in non-motile cilium assembly. Acts upstream of or within cilium assembly. Located in several cellular components, including cytosol; microtubule cytoskeleton; and non-motile cilium. Part of ciliary transition fiber. [provided by Alliance of Genome Resources, Apr 2022]

CEP89 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP89	NM_032816.5	c.1268+1832C>G		intron_variant	Intron 12 of 18	ENST00000305768.10	NP_116205.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP89	ENST00000305768.10	c.1268+1832C>G		intron_variant	Intron 12 of 18	1	NM_032816.5	ENSP00000306105.4
CEP89	ENST00000586984.6	n.1165-3268C>G		intron_variant	Intron 11 of 17	1		ENSP00000465141.1
CEP89	ENST00000591698.5	n.*602+1832C>G		intron_variant	Intron 11 of 17	2		ENSP00000467544.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41225 AN: 152062 Hom.: 5873 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.271 AC: 41257 AN: 152180 Hom.: 5877 Cov.: 33 AF XY: 0.274 AC XY: 20389 AN XY: 74412

African (AFR) AF: 0.255 AC: 10570 AN: 41524

American (AMR) AF: 0.306 AC: 4675 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1202 AN: 3472

East Asian (EAS) AF: 0.567 AC: 2932 AN: 5170

South Asian (SAS) AF: 0.386 AC: 1865 AN: 4826

European-Finnish (FIN) AF: 0.210 AC: 2224 AN: 10592

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16785 AN: 67998

Other (OTH) AF: 0.304 AC: 642 AN: 2110

Alfa AF: 0.248 Hom.: 675

Bravo AF: 0.278

Asia WGS AF: 0.434 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.63
PhyloP100		1.2
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: rs16967572; hg19: chr19-33412513;