9-121088492-G-A

Variant names:

• chr9-121088492-G-A
• rs10818503
• NM_007018.6:c.166G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007018.6(CNTRL):​c.166G>A​(p.Val56Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,610,020 control chromosomes in the GnomAD database, including 384,323 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (29106 hom., cov: 31)
  • Exomes 𝑓: 0.69 (355217 hom.)
• Consequence: CNTRL NM_007018.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847
• Publications: 43 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.2518924E-7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTRL	NM_007018.6	c.166G>A	p.Val56Ile	missense_variant	Exon 3 of 44	ENST00000373855.7	NP_008949.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTRL	ENST00000373855.7	c.166G>A	p.Val56Ile	missense_variant	Exon 3 of 44	5	NM_007018.6	ENSP00000362962.1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90398 AN: 151822 Hom.: 29085 Cov.: 31

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.632

GnomAD2 exomes AF: 0.704 AC: 176892 AN: 251178 AF XY: 0.715

Gnomad AFR exome AF: 0.322

Gnomad AMR exome AF: 0.833

Gnomad ASJ exome AF: 0.695

Gnomad EAS exome AF: 0.786

Gnomad FIN exome AF: 0.620

Gnomad NFE exome AF: 0.679

Gnomad OTH exome AF: 0.699

GnomAD4 exome AF: 0.693 AC: 1010429 AN: 1458080 Hom.: 355217 Cov.: 38 AF XY: 0.699 AC XY: 506934 AN XY: 725556

African (AFR) AF: 0.323 AC: 10803 AN: 33406

American (AMR) AF: 0.821 AC: 36726 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 18032 AN: 26110

East Asian (EAS) AF: 0.774 AC: 30702 AN: 39656

South Asian (SAS) AF: 0.870 AC: 74996 AN: 86178

European-Finnish (FIN) AF: 0.624 AC: 33340 AN: 53404

Middle Eastern (MID) AF: 0.730 AC: 4210 AN: 5764

European-Non Finnish (NFE) AF: 0.686 AC: 760337 AN: 1108594

Other (OTH) AF: 0.685 AC: 41283 AN: 60260

GnomAD4 genome AF: 0.595 AC: 90459 AN: 151940 Hom.: 29106 Cov.: 31 AF XY: 0.602 AC XY: 44718 AN XY: 74246

African (AFR) AF: 0.333 AC: 13787 AN: 41432

American (AMR) AF: 0.732 AC: 11181 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2350 AN: 3466

East Asian (EAS) AF: 0.771 AC: 3978 AN: 5160

South Asian (SAS) AF: 0.877 AC: 4220 AN: 4814

European-Finnish (FIN) AF: 0.637 AC: 6702 AN: 10526

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46027 AN: 67958

Other (OTH) AF: 0.632 AC: 1331 AN: 2106

Alfa AF: 0.661 Hom.: 119545

Bravo AF: 0.591

TwinsUK AF: 0.684 AC: 2537

ALSPAC AF: 0.687 AC: 2648

ESP6500AA AF: 0.336 AC: 1479

ESP6500EA AF: 0.690 AC: 5930

ExAC AF: 0.693 AC: 84155

Asia WGS AF: 0.752 AC: 2615 AN: 3478

EpiCase AF: 0.693

EpiControl AF: 0.691

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.018	T;T;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.43	T;.;T
MetaRNN	Benign	7.3e-7	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;M;M
PhyloP100		0.85
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.14	N;N;N
REVEL	Benign	0.026
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.51	T;T;T
Polyphen		0.0010	.;B;B
Vest4		0.016, 0.032
MPC		0.044
ClinPred		0.0031	T
GERP RS		2.6
Varity_R		0.035
gMVP		0.088
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10818503; hg19: chr9-123850770; COSMIC: COSV53042713;