rs12685539

Variant names:

• chr9-121094647-T-G
• rs12685539
• NM_007018.6:c.349-241T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 (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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007018.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTRL	NM_007018.6	MANE Select	c.349-241T>G		intron	N/A	NP_008949.4
	CNTRL	NM_001369893.1		c.349-241T>G		intron	N/A	NP_001356822.1	Q5JVD1
	CNTRL	NM_001369894.1		c.349-241T>G		intron	N/A	NP_001356823.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTRL	ENST00000373855.7	TSL:5 MANE Select	c.349-241T>G		intron	N/A	ENSP00000362962.1	Q7Z7A1-1
	CNTRL	ENST00000373847.6	TSL:1	c.349-241T>G		intron	N/A	ENSP00000362953.2	Q5JVD1
	CNTRL	ENST00000934490.1		c.349-241T>G		intron	N/A	ENSP00000604549.1

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

African (AFR) AF: 0.00286 AC: 119 AN: 41556

American (AMR) AF: 0.00320 AC: 49 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0309 AC: 160 AN: 5180

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4820

European-Finnish (FIN) AF: 0.0145 AC: 154 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0109 AC: 743 AN: 68018

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00909 Hom.: 6

Bravo AF: 0.00721

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

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: rs12685539; hg19: chr9-123856925;