17-7944637-C-A

Variant names:

• chr17-7944637-C-A
• rs11650083
• NM_053051.5:c.1733C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053051.5(CNTROB):​c.1733C>A​(p.Pro578Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 1,604,892 control chromosomes in the GnomAD database, including 203,968 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (19350 hom., cov: 32)
  • Exomes 𝑓: 0.50 (184618 hom.)
• Consequence: CNTROB NM_053051.5 missense, splice_region
• Scores: Splicing: ADA: 0.0009281
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 40 publications found

Genes affected

CNTROB (HGNC:29616): (centrobin, centriole duplication and spindle assembly protein) This gene encodes a centrosomal protein that interacts with BRCA2, and is required for centriole duplication and cytokinesis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0731001E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTROB	NM_053051.5	c.1733C>A	p.Pro578Gln	missense_variant, splice_region_variant	Exon 12 of 19	ENST00000563694.6	NP_444279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTROB	ENST00000563694.6	c.1733C>A	p.Pro578Gln	missense_variant, splice_region_variant	Exon 12 of 19	1	NM_053051.5	ENSP00000456335.1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75543 AN: 151902 Hom.: 19327 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.493

GnomAD2 exomes AF: 0.555 AC: 137342 AN: 247276 AF XY: 0.557

Gnomad AFR exome AF: 0.457

Gnomad AMR exome AF: 0.700

Gnomad ASJ exome AF: 0.445

Gnomad EAS exome AF: 0.766

Gnomad FIN exome AF: 0.549

Gnomad NFE exome AF: 0.460

Gnomad OTH exome AF: 0.505

GnomAD4 exome AF: 0.496 AC: 721250 AN: 1452872 Hom.: 184618 Cov.: 49 AF XY: 0.502 AC XY: 362370 AN XY: 721620

African (AFR) AF: 0.456 AC: 15136 AN: 33190

American (AMR) AF: 0.689 AC: 29989 AN: 43548

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 11208 AN: 25752

East Asian (EAS) AF: 0.747 AC: 29478 AN: 39460

South Asian (SAS) AF: 0.720 AC: 61772 AN: 85834

European-Finnish (FIN) AF: 0.545 AC: 29041 AN: 53282

Middle Eastern (MID) AF: 0.449 AC: 2414 AN: 5380

European-Non Finnish (NFE) AF: 0.462 AC: 511686 AN: 1106520

Other (OTH) AF: 0.510 AC: 30526 AN: 59906

GnomAD4 genome AF: 0.497 AC: 75611 AN: 152020 Hom.: 19350 Cov.: 32 AF XY: 0.508 AC XY: 37735 AN XY: 74308

African (AFR) AF: 0.458 AC: 18981 AN: 41454

American (AMR) AF: 0.595 AC: 9094 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1557 AN: 3464

East Asian (EAS) AF: 0.760 AC: 3923 AN: 5162

South Asian (SAS) AF: 0.725 AC: 3496 AN: 4822

European-Finnish (FIN) AF: 0.541 AC: 5714 AN: 10568

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31294 AN: 67954

Other (OTH) AF: 0.499 AC: 1053 AN: 2112

Alfa AF: 0.474 Hom.: 64390

Bravo AF: 0.495

TwinsUK AF: 0.457 AC: 1696

ALSPAC AF: 0.471 AC: 1816

ESP6500AA AF: 0.473 AC: 2082

ESP6500EA AF: 0.460 AC: 3952

ExAC AF: 0.548 AC: 66501

Asia WGS AF: 0.749 AC: 2604 AN: 3478

EpiCase AF: 0.447

EpiControl AF: 0.442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.8
DANN	Benign	0.48
DEOGEN2	Benign	0.0039	.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.54	T;T;T
MetaRNN	Benign	0.0000011	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.6	L;L;L
PhyloP100		-0.18
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.16	N;N;N
REVEL	Benign	0.029
Sift	Benign	0.63	T;T;T
Sift4G	Benign	0.49	T;T;T
Polyphen		0.0050	B;B;B
Vest4		0.082
MPC		0.33
ClinPred		0.0070	T
GERP RS		-2.4
Varity_R		0.017
gMVP		0.093
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00093
dbscSNV1_RF	Benign	0.16
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: rs11650083; hg19: chr17-7847955; COSMIC: COSV66609304; COSMIC: COSV66609304;