19-32921942-G-A

Variant names:

• chr19-32921942-G-A
• rs12983019
• NM_032816.5:c.1268+1497C>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.1268+1497C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,156 control chromosomes in the GnomAD database, including 3,918 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 0.22 (3918 hom., cov: 33)
• Consequence: CEP89 NM_032816.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 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.1268+1497C>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.1268+1497C>T		intron	N/A	ENSP00000306105.4
	CEP89	ENST00000586984.6	TSL:1	n.1165-3603C>T		intron	N/A	ENSP00000465141.1
	CEP89	ENST00000591698.5	TSL:2	n.*602+1497C>T		intron	N/A	ENSP00000467544.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33474 AN: 152038 Hom.: 3913 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.220 AC: 33505 AN: 152156 Hom.: 3918 Cov.: 33 AF XY: 0.222 AC XY: 16509 AN XY: 74378

African (AFR) AF: 0.223 AC: 9244 AN: 41512

American (AMR) AF: 0.244 AC: 3723 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3468

East Asian (EAS) AF: 0.512 AC: 2650 AN: 5172

South Asian (SAS) AF: 0.241 AC: 1162 AN: 4826

European-Finnish (FIN) AF: 0.198 AC: 2094 AN: 10590

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13102 AN: 67988

Other (OTH) AF: 0.233 AC: 493 AN: 2114

Alfa AF: 0.203 Hom.: 533

Bravo AF: 0.227

Asia WGS AF: 0.331 AC: 1152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		0.20
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: rs12983019; hg19: chr19-33412848;