9-121122028-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007018.6(CNTRL):c.1651-1903A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 603,460 control chromosomes in the GnomAD database, including 135,396 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 0.60 (29231 hom., cov: 32)
  • Exomes 𝑓: 0.68 (106165 hom.)
• Consequence: CNTRL NM_007018.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTRL	NM_007018.6	c.1651-1903A>G		intron_variant		ENST00000373855.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTRL	ENST00000373855.7	c.1651-1903A>G		intron_variant		5	NM_007018.6

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90593 AN: 151940 Hom.: 29212 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.633

GnomAD4 exome AF: 0.679 AC: 306664 AN: 451402 Hom.: 106165 AF XY: 0.680 AC XY: 144632 AN XY: 212630

Gnomad4 AFR exome AF: 0.298

Gnomad4 AMR exome AF: 0.797

Gnomad4 ASJ exome AF: 0.683

Gnomad4 EAS exome AF: 0.785

Gnomad4 SAS exome AF: 0.882

Gnomad4 FIN exome AF: 0.632

Gnomad4 NFE exome AF: 0.682

Gnomad4 OTH exome AF: 0.693

GnomAD4 genome AF: 0.596 AC: 90652 AN: 152058 Hom.: 29231 Cov.: 32 AF XY: 0.603 AC XY: 44852 AN XY: 74324

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.894

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.633

Alfa AF: 0.513 Hom.: 2146

Bravo AF: 0.591

Asia WGS AF: 0.768 AC: 2669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	6.4
Dann	Benign	0.71

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: rs10081760; hg19: chr9-123884306;