Variant 3-138500410-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_024491.4(CEP70):c.1526T>A(p.Leu509His) variant causes a missense change. The variant allele was found at a frequency of 0.002 in 1,584,810 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 7 hom. )

Consequence

CEP70
NM_024491.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.87

Variant links:

Genes affected

CEP70 (HGNC:29972): (centrosomal protein 70) Enables identical protein binding activity. Predicted to be involved in cilium assembly and regulation of microtubule cytoskeleton organization. Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

CEP70 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024000973).

BP6

Variant 3-138500410-A-T is Benign according to our data. Variant chr3-138500410-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654190.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP70	NM_024491.4 linkuse as main transcript	c.1526T>A	p.Leu509His	missense_variant	15/18	ENST00000264982.8	NP_077817.2	Q8NHQ1-1A0A140VJG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP70	ENST00000264982.8 linkuse as main transcript	c.1526T>A	p.Leu509His	missense_variant	15/18	1	NM_024491.4	ENSP00000264982.3		Q8NHQ1-1

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

208

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00222

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00157

AC:

352

AN:

224910

Hom.:

AF XY:

0.00160

AC XY:

195

AN XY:

121736

show subpopulations

Gnomad AFR exome

AF:

0.000445

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.00351

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000403

Gnomad FIN exome

AF:

0.000289

Gnomad NFE exome

AF:

0.00237

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00206

AC:

2957

AN:

1432528

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

1469

AN XY:

711644

show subpopulations

Gnomad4 AFR exome

AF:

0.000349

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00351

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000251

Gnomad4 FIN exome

AF:

0.000322

Gnomad4 NFE exome

AF:

0.00244

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00137

AC:

208

AN:

152282

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00222

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00186

Hom.:

Bravo

AF:

0.00146

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00140

AC:

170

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

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

CEP70: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

T;.;T;.;.

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

.;T;T;T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.024

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.6

M;.;M;.;M

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-4.3

D;D;D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D;D

Polyphen

0.043

B;B;B;.;D

Vest4

0.69

MVP

0.55

MPC

0.33

ClinPred

0.081

GERP RS

3.7

Varity_R

0.42

gMVP

0.49

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

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