rs7253624

Positions:

• chr19-32945381-G-A
• chr19-32945381-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.595+2885C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 151,954 control chromosomes in the GnomAD database, including 1,352 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 0.13 (1352 hom., cov: 31)
• Consequence: CEP89 NM_032816.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP89	NM_032816.5	c.595+2885C>T		intron_variant		ENST00000305768.10
CEP89	XM_005259344.4	c.595+2885C>T		intron_variant
CEP89	XM_017027398.2	c.595+2885C>T		intron_variant
CEP89	XM_047439563.1	c.595+2885C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP89	ENST00000305768.10	c.595+2885C>T		intron_variant		1	NM_032816.5	P3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19774 AN: 151860 Hom.: 1347 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.130 AC: 19789 AN: 151954 Hom.: 1352 Cov.: 31 AF XY: 0.131 AC XY: 9691 AN XY: 74238

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.129

Alfa AF: 0.123 Hom.: 305

Bravo AF: 0.132

Asia WGS AF: 0.151 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.3
DANN	Benign	0.21

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: rs7253624; hg19: chr19-33436287;