rs147018954

Variant names:

• chr9-121088364-C-A
• rs147018954
• NM_007018.6:c.38C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-121088364-C-A
• chr9-121088364-C-G
• chr9-121088364-C-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_007018.6(CNTRL):​c.38C>A​(p.Ala13Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,613,364 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (17 hom.)
• Consequence: CNTRL NM_007018.6 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.91
• Publications: 8 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005883783).
• BP6: Variant 9-121088364-C-A is Benign according to our data. Variant chr9-121088364-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 719912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 17 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.38C>A	p.Ala13Glu	missense	Exon 3 of 44	NP_008949.4
	CNTRL	NM_001369893.1		c.38C>A	p.Ala13Glu	missense	Exon 2 of 32	NP_001356822.1	Q5JVD1
	CNTRL	NM_001369894.1		c.38C>A	p.Ala13Glu	missense	Exon 2 of 30	NP_001356823.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTRL	ENST00000373855.7	TSL:5 MANE Select	c.38C>A	p.Ala13Glu	missense	Exon 3 of 44	ENSP00000362962.1	Q7Z7A1-1
	CNTRL	ENST00000373847.6	TSL:1	c.38C>A	p.Ala13Glu	missense	Exon 2 of 32	ENSP00000362953.2	Q5JVD1
	CNTRL	ENST00000934490.1		c.38C>A	p.Ala13Glu	missense	Exon 3 of 43	ENSP00000604549.1

Frequencies

GnomAD3 genomes AF: 0.00216 AC: 329 AN: 152160 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00338

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00204 AC: 512 AN: 251220 AF XY: 0.00211

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00371

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00308

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00312 AC: 4560 AN: 1461086 Hom.: 17 Cov.: 29 AF XY: 0.00297 AC XY: 2161 AN XY: 726924

African (AFR) AF: 0.000926 AC: 31 AN: 33466

American (AMR) AF: 0.00438 AC: 196 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000459 AC: 12 AN: 26122

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39664

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86220

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53414

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.00373 AC: 4149 AN: 1111360

Other (OTH) AF: 0.00258 AC: 156 AN: 60372

GnomAD4 genome AF: 0.00216 AC: 329 AN: 152278 Hom.: 1 Cov.: 32 AF XY: 0.00187 AC XY: 139 AN XY: 74462

African (AFR) AF: 0.000866 AC: 36 AN: 41564

American (AMR) AF: 0.00353 AC: 54 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10602

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

European-Non Finnish (NFE) AF: 0.00338 AC: 230 AN: 68016

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00304 Hom.: 1

Bravo AF: 0.00297

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00360 AC: 31

ExAC AF: 0.00181 AC: 220

EpiCase AF: 0.00393

EpiControl AF: 0.00350

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.017
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.0059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M
PhyloP100		1.9
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.049
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.017	D
Polyphen		0.18	B
Vest4		0.10
MVP		0.27
MPC		0.085
ClinPred		0.023	T
GERP RS		5.8
Varity_R		0.23
gMVP		0.20
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: rs147018954; hg19: chr9-123850642; COSMIC: COSV99440661;