19-32923139-G-C

Variant names:

• chr19-32923139-G-C
• rs3795058
• NM_032816.5:c.1268+300C>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+300C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,888 control chromosomes in the GnomAD database, including 12,943 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 0.41 (12943 hom., cov: 31)
• Consequence: CEP89 NM_032816.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP89	NM_032816.5	c.1268+300C>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+300C>G		intron_variant	Intron 12 of 18	1	NM_032816.5	ENSP00000306105.4
CEP89	ENST00000586984.6	n.1164+3051C>G		intron_variant	Intron 11 of 17	1		ENSP00000465141.1
CEP89	ENST00000591698.5	n.*602+300C>G		intron_variant	Intron 11 of 17	2		ENSP00000467544.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61735 AN: 151770 Hom.: 12927 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.407 AC: 61783 AN: 151888 Hom.: 12943 Cov.: 31 AF XY: 0.411 AC XY: 30509 AN XY: 74226

African (AFR) AF: 0.418 AC: 17310 AN: 41400

American (AMR) AF: 0.384 AC: 5849 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1383 AN: 3470

East Asian (EAS) AF: 0.739 AC: 3811 AN: 5160

South Asian (SAS) AF: 0.408 AC: 1965 AN: 4822

European-Finnish (FIN) AF: 0.468 AC: 4926 AN: 10532

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.371 AC: 25228 AN: 67936

Other (OTH) AF: 0.421 AC: 891 AN: 2114

Alfa AF: 0.385 Hom.: 1409

Bravo AF: 0.404

Asia WGS AF: 0.556 AC: 1932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.21
DANN	Benign	0.61
PhyloP100		-0.80
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: rs3795058; hg19: chr19-33414045;