Variant 9-121088364-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_007018.6(CNTRL):c.38C>A(p.Ala13Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,613,364 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 17 hom. )

Consequence

CNTRL
NM_007018.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.91

Variant links:

Genes affected

CNTRL (HGNC:1858): (centriolin) This gene encodes a centrosomal protein required for the centrosome to function as a microtubule organizing center. The gene product is also associated with centrosome maturation. One version of stem cell myeloproliferative disorder is the result of a reciprocal translocation between chromosomes 8 and 9, with the breakpoint associated with fibroblast growth factor receptor 1 and centrosomal protein 1. [provided by RefSeq, Jul 2008]

CNTRL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005883783).

BP6

Variant 9-121088364-C-A is Benign according to our data. Variant chr9-121088364-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 719912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTRL	NM_007018.6 linkuse as main transcript	c.38C>A	p.Ala13Glu	missense_variant	3/44	ENST00000373855.7	NP_008949.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTRL	ENST00000373855.7 linkuse as main transcript	c.38C>A	p.Ala13Glu	missense_variant	3/44	5	NM_007018.6	ENSP00000362962		Q7Z7A1-1

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

329

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00354

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00338

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00204

AC:

512

AN:

251220

Hom.:

AF XY:

0.00211

AC XY:

286

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00371

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00308

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00312

AC:

4560

AN:

1461086

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

2161

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00438

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00373

Gnomad4 OTH exome

AF:

0.00258

GnomAD4 genome

AF:

0.00216

AC:

329

AN:

152278

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00338

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00313

Hom.:

Bravo

AF:

0.00297

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00181

AC:

220

EpiCase

AF:

0.00393

EpiControl

AF:

0.00350

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 11, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.022

T;T;T

Eigen

Benign

-0.017

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.72

T;.;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.0059

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;M;M

MutationTaster

Benign

0.86

D;D;D

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.78

N;N;N

REVEL

Benign

0.049

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.017

D;D;D

Polyphen

0.18

.;B;B

Vest4

0.10, 0.11

MVP

0.27

MPC

0.085

ClinPred

0.023

GERP RS

5.8

Varity_R

0.23

gMVP

0.20

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