rs7253624

Variant names:

• chr19-32945381-G-A
• rs7253624
• NM_032816.5:c.595+2885C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-32945381-G-A
• chr19-32945381-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032816.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP89	NM_032816.5	MANE Select	c.595+2885C>T		intron	N/A	NP_116205.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP89	ENST00000305768.10	TSL:1 MANE Select	c.595+2885C>T		intron	N/A	ENSP00000306105.4	Q96ST8-1
	CEP89	ENST00000590597.6	TSL:1	c.595+2885C>T		intron	N/A	ENSP00000466442.1	A0A0C4DGP8
	CEP89	ENST00000593276.2	TSL:1	c.508+2885C>T		intron	N/A	ENSP00000467839.1	K7EQI2

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

African (AFR) AF: 0.106 AC: 4381 AN: 41428

American (AMR) AF: 0.148 AC: 2256 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3468

East Asian (EAS) AF: 0.287 AC: 1478 AN: 5158

South Asian (SAS) AF: 0.103 AC: 498 AN: 4822

European-Finnish (FIN) AF: 0.137 AC: 1447 AN: 10528

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.129 AC: 8774 AN: 67976

Other (OTH) AF: 0.129 AC: 273 AN: 2110

Alfa AF: 0.122 Hom.: 453

Bravo AF: 0.132

Asia WGS AF: 0.151 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.3
DANN	Benign	0.21
PhyloP100		0.021
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: rs7253624; hg19: chr19-33436287;