9-121122028-A-G

Variant names:

• chr9-121122028-A-G
• rs10081760
• NM_007018.6:c.1651-1903A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.59).
• 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 rank	MANE	Protein	UniProt
CNTRL	NM_007018.6	c.1651-1903A>G		intron_variant	Intron 12 of 43	ENST00000373855.7	NP_008949.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTRL	ENST00000373855.7	c.1651-1903A>G		intron_variant	Intron 12 of 43	5	NM_007018.6	ENSP00000362962.1

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

African (AFR) AF: 0.298 AC: 2542 AN: 8530

American (AMR) AF: 0.797 AC: 373 AN: 468

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 1904 AN: 2786

East Asian (EAS) AF: 0.785 AC: 1431 AN: 1824

South Asian (SAS) AF: 0.882 AC: 7651 AN: 8672

European-Finnish (FIN) AF: 0.632 AC: 91 AN: 144

Middle Eastern (MID) AF: 0.744 AC: 696 AN: 936

European-Non Finnish (NFE) AF: 0.682 AC: 281737 AN: 413264

Other (OTH) AF: 0.693 AC: 10239 AN: 14778

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

African (AFR) AF: 0.333 AC: 13793 AN: 41424

American (AMR) AF: 0.732 AC: 11180 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2355 AN: 3472

East Asian (EAS) AF: 0.770 AC: 3985 AN: 5178

South Asian (SAS) AF: 0.894 AC: 4318 AN: 4830

European-Finnish (FIN) AF: 0.637 AC: 6725 AN: 10562

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46070 AN: 67990

Other (OTH) AF: 0.633 AC: 1338 AN: 2114

Alfa AF: 0.503 Hom.: 2191

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
PhyloP100		-0.17
PromoterAI		0.10	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs10081760; hg19: chr9-123884306;