Genetic Variant CEP295:c.625-16T>C (chr11-93679396-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_033395.2(CEP295):c.625-16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00477 in 1,533,410 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 43 hom. )

Consequence

CEP295
NM_033395.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.220

Publications

0 publications found

Variant links:

Genes affected

CEP295 (HGNC:29366): (centrosomal protein 295) Enables microtubule binding activity. Involved in several processes, including centriole replication; positive regulation of protein acetylation; and regulation of centrosome duplication. Located in cytosol; microtubule cytoskeleton; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CEP295 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 11-93679396-T-C is Benign according to our data. Variant chr11-93679396-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3770499.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP295	NM_033395.2 link	c.625-16T>C		intron_variant	Intron 6 of 29	ENST00000325212.11	NP_203753.1	Q9C0D2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP295	ENST00000325212.11 link	c.625-16T>C		intron_variant	Intron 6 of 29	2	NM_033395.2	ENSP00000316681.6		Q9C0D2-1

Frequencies

GnomAD3 genomes

AF:

0.00443

AC:

674

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00688

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00611

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00521

AC:

735

AN:

141160

AF XY:

0.00552

show subpopulations

Gnomad AFR exome

AF:

0.000392

Gnomad AMR exome

AF:

0.00331

Gnomad ASJ exome

AF:

0.0267

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00834

Gnomad NFE exome

AF:

0.00491

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00480

AC:

6635

AN:

1381078

Hom.:

Cov.:

AF XY:

0.00487

AC XY:

3315

AN XY:

680658

show subpopulations

African (AFR)

AF:

0.000522

AC:

AN:

30642

American (AMR)

AF:

0.00322

AC:

101

AN:

31326

Ashkenazi Jewish (ASJ)

AF:

0.0269

AC:

652

AN:

24274

East Asian (EAS)

AF:

0.00

AC:

AN:

35530

South Asian (SAS)

AF:

0.00138

AC:

104

AN:

75190

European-Finnish (FIN)

AF:

0.00944

AC:

462

AN:

48958

Middle Eastern (MID)

AF:

0.000536

AC:

AN:

5598

European-Non Finnish (NFE)

AF:

0.00460

AC:

4937

AN:

1072338

Other (OTH)

AF:

0.00629

AC:

360

AN:

57222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

307

613

920

1226

1533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00442

AC:

674

AN:

152332

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

319

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000818

AC:

AN:

41582

American (AMR)

AF:

0.00189

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0294

AC:

102

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00124

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00688

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00612

AC:

416

AN:

68026

Other (OTH)

AF:

0.00662

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00709

Hom.:

Bravo

AF:

0.00355

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CEP295: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

(source)

DANN

Benign

0.51

PhyloP100

0.22

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: -40

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr11-93679396-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over