NM_032816.5:c.1384+1177G>C

Variant names:

• chr19-32917047-C-G
• rs7253595
• NM_032816.5:c.1384+1177G>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.1384+1177G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,258 control chromosomes in the GnomAD database, including 62,237 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 (62237 hom., cov: 31)
• Consequence: CEP89 NM_032816.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 10 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.968 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP89	NM_032816.5	MANE Select	c.1384+1177G>C		intron	N/A	NP_116205.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP89	ENST00000305768.10	TSL:1 MANE Select	c.1384+1177G>C		intron	N/A	ENSP00000306105.4
	CEP89	ENST00000586984.6	TSL:1	n.1280+1177G>C		intron	N/A	ENSP00000465141.1
	CEP89	ENST00000591698.5	TSL:2	n.*718+1177G>C		intron	N/A	ENSP00000467544.1

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137340 AN: 152140 Hom.: 62172 Cov.: 31

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.884

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

GnomAD4 genome AF: 0.903 AC: 137466 AN: 152258 Hom.: 62237 Cov.: 31 AF XY: 0.905 AC XY: 67339 AN XY: 74432

African (AFR) AF: 0.976 AC: 40566 AN: 41560

American (AMR) AF: 0.917 AC: 14031 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2889 AN: 3472

East Asian (EAS) AF: 0.898 AC: 4656 AN: 5184

South Asian (SAS) AF: 0.948 AC: 4566 AN: 4816

European-Finnish (FIN) AF: 0.889 AC: 9416 AN: 10596

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.860 AC: 58492 AN: 68016

Other (OTH) AF: 0.885 AC: 1870 AN: 2112

Alfa AF: 0.878 Hom.: 3301

Bravo AF: 0.905

Asia WGS AF: 0.936 AC: 3254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.55
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7253595; hg19: chr19-33407953;