19-32962753-T-C

Position:

• chr19-32962753-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032816.5(CEP89):​c.147-2695A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 152,238 control chromosomes in the GnomAD database, including 61,963 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 0.90 (61963 hom., cov: 32)
• Consequence: CEP89 NM_032816.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819

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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP89	NM_032816.5	c.147-2695A>G		intron_variant		ENST00000305768.10	NP_116205.3
CEP89	XM_005259344.4	c.147-2695A>G		intron_variant			XP_005259401.1
CEP89	XM_017027398.2	c.147-2695A>G		intron_variant			XP_016882887.1
CEP89	XM_047439563.1	c.147-2695A>G		intron_variant			XP_047295519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP89	ENST00000305768.10	c.147-2695A>G		intron_variant		1	NM_032816.5	ENSP00000306105.4
CEP89	ENST00000590597.6	c.147-2695A>G		intron_variant		1		ENSP00000466442.1
CEP89	ENST00000593276.2	c.60-2695A>G		intron_variant		1		ENSP00000467839.1
CEP89	ENST00000586984.6	n.147-2695A>G		intron_variant		1		ENSP00000465141.1

Frequencies

GnomAD3 genomes AF: 0.901 AC: 137014 AN: 152120 Hom.: 61898 Cov.: 32

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.882

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

GnomAD4 genome AF: 0.901 AC: 137140 AN: 152238 Hom.: 61963 Cov.: 32 AF XY: 0.903 AC XY: 67186 AN XY: 74416

Gnomad4 AFR AF: 0.976

Gnomad4 AMR AF: 0.916

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.897

Gnomad4 SAS AF: 0.947

Gnomad4 FIN AF: 0.889

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.884

Alfa AF: 0.860 Hom.: 101076

Bravo AF: 0.903

Asia WGS AF: 0.935 AC: 3251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	3.6
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs4805834; hg19: chr19-33453659;