rs17272267

Variant names:

• chr19-32880287-G-A
• rs17272267
• NM_032816.5:c.2136-909C>T

Variant summary

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

The NM_032816.5(CEP89):​c.2136-909C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,202 control chromosomes in the GnomAD database, including 2,002 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 0.15 (2002 hom., cov: 33)
• Consequence: CEP89 NM_032816.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032816.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP89	NM_032816.5	MANE Select	c.2136-909C>T		intron	N/A	NP_116205.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP89	ENST00000305768.10	TSL:1 MANE Select	c.2136-909C>T		intron	N/A	ENSP00000306105.4
	CEP89	ENST00000586984.6	TSL:1	n.*745-909C>T		intron	N/A	ENSP00000465141.1
	CEP89	ENST00000591698.5	TSL:2	n.*1470-909C>T		intron	N/A	ENSP00000467544.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22299 AN: 152084 Hom.: 2000 Cov.: 33

Gnomad AFR AF: 0.0677

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.147 AC: 22300 AN: 152202 Hom.: 2002 Cov.: 33 AF XY: 0.142 AC XY: 10591 AN XY: 74394

African (AFR) AF: 0.0676 AC: 2811 AN: 41554

American (AMR) AF: 0.111 AC: 1691 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3472

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5186

South Asian (SAS) AF: 0.158 AC: 759 AN: 4810

European-Finnish (FIN) AF: 0.175 AC: 1851 AN: 10580

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14400 AN: 67990

Other (OTH) AF: 0.123 AC: 260 AN: 2114

Alfa AF: 0.160 Hom.: 449

Bravo AF: 0.136

Asia WGS AF: 0.0650 AC: 225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.66
PhyloP100		0.061
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: rs17272267; hg19: chr19-33371193; COSMIC: COSV59867185; COSMIC: COSV59867185;