Variant chr19-32879164-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_032816.5(CEP89):c.2350T>C(p.Ter784GlnextTer8) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,602,036 control chromosomes in the GnomAD database, including 89,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5492 hom., cov: 32)

Exomes 𝑓: 0.33 ( 83569 hom. )

Consequence

CEP89
NM_032816.5 stop_lost

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.919

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM4

Stoplost variant in NM_032816.5 Downstream stopcodon found after 4 codons.

BP6

Variant 19-32879164-A-G is Benign according to our data. Variant chr19-32879164-A-G is described in ClinVar as [Benign]. Clinvar id is 1669354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CEP89	NM_032816.5 linkuse as main transcript	c.2350T>C	p.Ter784GlnextTer8	stop_lost	19/19	ENST00000305768.10
CEP89	XM_005259344.4 linkuse as main transcript	c.2278T>C	p.Ter760GlnextTer8	stop_lost	19/19
CEP89	XM_047439562.1 linkuse as main transcript	c.1609T>C	p.Ter537GlnextTer8	stop_lost	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP89	ENST00000305768.10 linkuse as main transcript	c.2350T>C	p.Ter784GlnextTer8	stop_lost	19/19	1	NM_032816.5	P3	Q96ST8-1
CEP89	ENST00000586984.6 linkuse as main transcript	c.*959T>C		3_prime_UTR_variant, NMD_transcript_variant	18/18	1
CEP89	ENST00000591698.5 linkuse as main transcript	c.*1684T>C		3_prime_UTR_variant, NMD_transcript_variant	18/18	2

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37529

AN:

151930

Hom.:

5495

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.352

Gnomad OTH

AF:

0.244

GnomAD3 exomes

AF:

0.261

AC:

64342

AN:

246806

Hom.:

9611

AF XY:

0.268

AC XY:

35699

AN XY:

133294

show subpopulations

Gnomad AFR exome

AF:

0.0979

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.287

Gnomad EAS exome

AF:

0.117

Gnomad SAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.305

Gnomad NFE exome

AF:

0.349

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.329

AC:

476806

AN:

1449988

Hom.:

83569

Cov.:

AF XY:

0.326

AC XY:

234683

AN XY:

720182

show subpopulations

Gnomad4 AFR exome

AF:

0.0931

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.0922

Gnomad4 SAS exome

AF:

0.209

Gnomad4 FIN exome

AF:

0.306

Gnomad4 NFE exome

AF:

0.365

Gnomad4 OTH exome

AF:

0.302

GnomAD4 genome

AF:

0.247

AC:

37525

AN:

152048

Hom.:

5492

Cov.:

AF XY:

0.241

AC XY:

17900

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.287

Gnomad4 EAS

AF:

0.108

Gnomad4 SAS

AF:

0.210

Gnomad4 FIN

AF:

0.285

Gnomad4 NFE

AF:

0.352

Gnomad4 OTH

AF:

0.240

Alfa

AF:

0.324

Hom.:

21530

Bravo

AF:

0.234

TwinsUK

AF:

0.372

AC:

1378

ALSPAC

AF:

0.367

AC:

1415

ESP6500AA

AF:

0.109

AC:

480

ESP6500EA

AF:

0.355

AC:

3049

ExAC

AF:

0.264

AC:

32029

Asia WGS

AF:

0.131

AC:

457

AN:

3478

EpiCase

AF:

0.343

EpiControl

AF:

0.343

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.90

BayesDel_noAF

Benign

-0.92

CADD

Benign

5.3

DANN

Benign

0.60

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.00030

MutationTaster

Benign

1.0

Vest4

0.0070

GERP RS

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over