19-32923139-G-C

Position:

• chr19-32923139-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CEP89	NM_032816.5	c.1268+300C>G		intron_variant		ENST00000305768.10	NP_116205.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP89	ENST00000305768.10	c.1268+300C>G		intron_variant		1	NM_032816.5	ENSP00000306105.4
CEP89	ENST00000586984.6	n.1164+3051C>G		intron_variant		1		ENSP00000465141.1
CEP89	ENST00000591698.5	n.*602+300C>G		intron_variant		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

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.421

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3795058; hg19: chr19-33414045;