rs3736855

chr9-121154742-T-Achr9-121154742-T-G

Variant summary

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

The NM_007018.6(CNTRL):c.4194T>A(p.Val1398=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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=-0.53).
• 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/exons	MANE	UniProt
CNTRL	NM_007018.6	c.4194T>A	p.Val1398=	synonymous_variant	27/44	ENST00000373855.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTRL	ENST00000373855.7	c.4194T>A	p.Val1398=	synonymous_variant	27/44	5	NM_007018.6

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58319 AN: 151952 Hom.: 12658 Cov.: 32

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

GnomAD3 exomes AF: 0.472 AC: 118174 AN: 250396 Hom.: 29548 AF XY: 0.484 AC XY: 65483 AN XY: 135386

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 SAS exome AF: 0.652

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.: 30 AF XY: 0.454 AC XY: 326839 AN XY: 720184

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.540

Gnomad4 ASJ exome AF: 0.506

Gnomad4 EAS exome AF: 0.529

Gnomad4 SAS exome AF: 0.651

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.445

GnomAD4 genome AF: 0.384 AC: 58349 AN: 152070 Hom.: 12670 Cov.: 32 AF XY: 0.394 AC XY: 29270 AN XY: 74336

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.418

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
Dann	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs3736855; hg19: chr9-123917020; COSMIC: COSV53046956; COSMIC: COSV53046956;