rs12685539

Positions:

• chr9-121094647-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_007018.6(CNTRL):​c.349-241T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00816 in 152,270 control chromosomes in the GnomAD database, including 9 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 0.0082 (9 hom., cov: 31)
• Consequence: CNTRL NM_007018.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=-0.81).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00816 (1242/152270) while in subpopulation EAS AF= 0.0309 (160/5180). AF 95% confidence interval is 0.027. There are 9 homozygotes in gnomad4. There are 631 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTRL	NM_007018.6	c.349-241T>G		intron_variant		ENST00000373855.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTRL	ENST00000373855.7	c.349-241T>G		intron_variant		5	NM_007018.6

Frequencies

GnomAD3 genomes AF: 0.00817 AC: 1243 AN: 152152 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.00287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.00287

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00816 AC: 1242 AN: 152270 Hom.: 9 Cov.: 31 AF XY: 0.00847 AC XY: 631 AN XY: 74456

Gnomad4 AFR AF: 0.00286

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0309

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0145

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.0103 Hom.: 3

Bravo AF: 0.00721

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.66

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: rs12685539; hg19: chr9-123856925;