19-32962753-T-C

Variant names:

• chr19-32962753-T-C
• rs4805834
• NM_032816.5:c.147-2695A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 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=-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 rank	MANE	Protein	UniProt
CEP89	NM_032816.5	c.147-2695A>G		intron_variant	Intron 2 of 18	ENST00000305768.10	NP_116205.3
CEP89	XM_005259344.4	c.147-2695A>G		intron_variant	Intron 2 of 18		XP_005259401.1
CEP89	XM_017027398.2	c.147-2695A>G		intron_variant	Intron 2 of 16		XP_016882887.1
CEP89	XM_047439563.1	c.147-2695A>G		intron_variant	Intron 2 of 14		XP_047295519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP89	ENST00000305768.10	c.147-2695A>G		intron_variant	Intron 2 of 18	1	NM_032816.5	ENSP00000306105.4
CEP89	ENST00000590597.6	c.147-2695A>G		intron_variant	Intron 2 of 8	1		ENSP00000466442.1
CEP89	ENST00000593276.2	c.60-2695A>G		intron_variant	Intron 1 of 5	1		ENSP00000467839.1
CEP89	ENST00000586984.6	n.147-2695A>G		intron_variant	Intron 2 of 17	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

African (AFR) AF: 0.976 AC: 40543 AN: 41554

American (AMR) AF: 0.916 AC: 13989 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2848 AN: 3468

East Asian (EAS) AF: 0.897 AC: 4627 AN: 5156

South Asian (SAS) AF: 0.947 AC: 4573 AN: 4830

European-Finnish (FIN) AF: 0.889 AC: 9428 AN: 10610

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.857 AC: 58307 AN: 68022

Other (OTH) AF: 0.884 AC: 1866 AN: 2112

Alfa AF: 0.869 Hom.: 226469

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
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4805834; hg19: chr19-33453659;