9-121152596-C-T

Position:

• chr9-121152596-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007018.6(CNTRL):​c.4075C>T​(p.Leu1359=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 1,613,616 control chromosomes in the GnomAD database, including 2,267 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 0.039 (130 hom., cov: 32)
  • Exomes 𝑓: 0.051 (2137 hom.)
• Consequence: CNTRL NM_007018.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-0.81 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTRL	NM_007018.6	c.4075C>T	p.Leu1359=	synonymous_variant	26/44	ENST00000373855.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTRL	ENST00000373855.7	c.4075C>T	p.Leu1359=	synonymous_variant	26/44	5	NM_007018.6

Frequencies

GnomAD3 genomes AF: 0.0387 AC: 5885 AN: 152124 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0251

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.0501

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0549

Gnomad OTH AF: 0.0364

GnomAD3 exomes AF: 0.0378 AC: 9492 AN: 251192 Hom.: 233 AF XY: 0.0378 AC XY: 5125 AN XY: 135754

Gnomad AFR exome AF: 0.0240

Gnomad AMR exome AF: 0.0189

Gnomad ASJ exome AF: 0.0226

Gnomad EAS exome AF: 0.00147

Gnomad SAS exome AF: 0.0177

Gnomad FIN exome AF: 0.0550

Gnomad NFE exome AF: 0.0546

Gnomad OTH exome AF: 0.0421

GnomAD4 exome AF: 0.0506 AC: 73939 AN: 1461374 Hom.: 2137 Cov.: 31 AF XY: 0.0495 AC XY: 36014 AN XY: 727022

Gnomad4 AFR exome AF: 0.0219

Gnomad4 AMR exome AF: 0.0202

Gnomad4 ASJ exome AF: 0.0246

Gnomad4 EAS exome AF: 0.00504

Gnomad4 SAS exome AF: 0.0173

Gnomad4 FIN exome AF: 0.0557

Gnomad4 NFE exome AF: 0.0576

Gnomad4 OTH exome AF: 0.0464

GnomAD4 genome AF: 0.0387 AC: 5887 AN: 152242 Hom.: 130 Cov.: 32 AF XY: 0.0365 AC XY: 2718 AN XY: 74422

Gnomad4 AFR AF: 0.0230

Gnomad4 AMR AF: 0.0250

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.0156

Gnomad4 FIN AF: 0.0501

Gnomad4 NFE AF: 0.0549

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0496 Hom.: 505

Bravo AF: 0.0374

Asia WGS AF: 0.0150 AC: 52 AN: 3478

EpiCase AF: 0.0531

EpiControl AF: 0.0507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.6
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs9408926; hg19: chr9-123914874;