Genetic Variant CNTRL:p.Val1398Val (chr9-121154742-T-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_007018.6(CNTRL):c.4194T>A(p.Val1398Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,597,718 control chromosomes in the GnomAD database, including 161,749 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 0.38 ( 12670 hom., cov: 32)

Exomes 𝑓: 0.45 ( 149079 hom. )

Consequence

CNTRL
NM_007018.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0860

Publications

19 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP7

Synonymous conserved (PhyloP=0.086 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTRL	NM_007018.6 link	c.4194T>A	p.Val1398Val	synonymous_variant	Exon 27 of 44	ENST00000373855.7	NP_008949.4	Q7Z7A1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTRL	ENST00000373855.7 link	c.4194T>A	p.Val1398Val	synonymous_variant	Exon 27 of 44	5	NM_007018.6	ENSP00000362962.1		Q7Z7A1-1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58319

AN:

151952

Hom.:

12658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.600

Gnomad AMR

AF:

0.494

Gnomad ASJ

AF:

0.515

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.644

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.418

GnomAD2 exomes

AF:

0.472

AC:

118174

AN:

250396

AF XY:

0.484

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.544

Gnomad ASJ exome

AF:

0.510

Gnomad EAS exome

AF:

0.553

Gnomad FIN exome

AF:

0.465

Gnomad NFE exome

AF:

0.430

Gnomad OTH exome

AF:

0.466

GnomAD4 exome

AF:

0.447

AC:

645759

AN:

1445648

Hom.:

149079

Cov.:

AF XY:

0.454

AC XY:

326839

AN XY:

720184

show subpopulations

African (AFR)

AF:

0.164

AC:

5460

AN:

33294

American (AMR)

AF:

0.540

AC:

24099

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.506

AC:

13136

AN:

25986

East Asian (EAS)

AF:

0.529

AC:

20909

AN:

39546

South Asian (SAS)

AF:

0.651

AC:

55811

AN:

85732

European-Finnish (FIN)

AF:

0.462

AC:

24630

AN:

53326

Middle Eastern (MID)

AF:

0.508

AC:

2763

AN:

5442

European-Non Finnish (NFE)

AF:

0.430

AC:

472309

AN:

1097812

Other (OTH)

AF:

0.445

AC:

26642

AN:

59852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

15178

30355

45533

60710

75888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14356

28712

43068

57424

71780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.384

AC:

58349

AN:

152070

Hom.:

12670

Cov.:

AF XY:

0.394

AC XY:

29270

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.175

AC:

7241

AN:

41494

American (AMR)

AF:

0.494

AC:

7547

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.515

AC:

1787

AN:

3470

East Asian (EAS)

AF:

0.554

AC:

2863

AN:

5170

South Asian (SAS)

AF:

0.645

AC:

3112

AN:

4826

European-Finnish (FIN)

AF:

0.487

AC:

5145

AN:

10564

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.428

AC:

29089

AN:

67960

Other (OTH)

AF:

0.418

AC:

882

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1717

3434

5150

6867

8584

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.424

Hom.:

4667

Bravo

AF:

0.374

Asia WGS

AF:

0.541

AC:

1883

AN:

3478

EpiCase

AF:

0.440

EpiControl

AF:

0.434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.3

(source)

DANN

Benign

0.81

PhyloP100

0.086

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over