chr19-32921942-G-A

Position:

• chr19-32921942-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP89	NM_032816.5	c.1268+1497C>T		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+1497C>T		intron_variant		1	NM_032816.5	ENSP00000306105	P3
CEP89	ENST00000586984.6	c.1165-3603C>T		intron_variant, NMD_transcript_variant		1		ENSP00000465141
CEP89	ENST00000591698.5	c.*602+1497C>T		intron_variant, NMD_transcript_variant		2		ENSP00000467544

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

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.233

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.72

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: rs12983019; hg19: chr19-33412848;