rs226891

Positions:

• chr16-19536425-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001323572.2(CCP110):​c.756C>G​(p.Ile252Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 1,613,540 control chromosomes in the GnomAD database, including 651,781 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.91 (62994 hom., cov: 32)
  • Exomes 𝑓: 0.90 (588787 hom.)
• Consequence: CCP110 NM_001323572.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.06

Genes affected

CCP110 (HGNC:24342): (centriolar coiled-coil protein 110) Involved in centriole replication; negative regulation of cilium assembly; and regulation of cytokinesis. Located in centriole and centrosome. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.255988E-7).
• BP6: Variant 16-19536425-C-G is Benign according to our data. Variant chr16-19536425-C-G is described in ClinVar as [Benign]. Clinvar id is 402512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCP110	NM_001323572.2	c.756C>G	p.Ile252Met	missense_variant	4/14	ENST00000694978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCP110	ENST00000694978.1	c.756C>G	p.Ile252Met	missense_variant	4/14		NM_001323572.2	P4

Frequencies

GnomAD3 genomes AF: 0.908 AC: 138114 AN: 152170 Hom.: 62942 Cov.: 32

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.905

GnomAD3 exomes AF: 0.869 AC: 217675 AN: 250590 Hom.: 95625 AF XY: 0.861 AC XY: 116634 AN XY: 135540

Gnomad AFR exome AF: 0.952

Gnomad AMR exome AF: 0.862

Gnomad ASJ exome AF: 0.948

Gnomad EAS exome AF: 0.785

Gnomad SAS exome AF: 0.665

Gnomad FIN exome AF: 0.900

Gnomad NFE exome AF: 0.914

Gnomad OTH exome AF: 0.873

GnomAD4 exome AF: 0.895 AC: 1308305 AN: 1461252 Hom.: 588787 Cov.: 41 AF XY: 0.889 AC XY: 646020 AN XY: 726922

Gnomad4 AFR exome AF: 0.954

Gnomad4 AMR exome AF: 0.864

Gnomad4 ASJ exome AF: 0.949

Gnomad4 EAS exome AF: 0.813

Gnomad4 SAS exome AF: 0.674

Gnomad4 FIN exome AF: 0.900

Gnomad4 NFE exome AF: 0.914

Gnomad4 OTH exome AF: 0.885

GnomAD4 genome AF: 0.908 AC: 138222 AN: 152288 Hom.: 62994 Cov.: 32 AF XY: 0.903 AC XY: 67247 AN XY: 74462

Gnomad4 AFR AF: 0.951

Gnomad4 AMR AF: 0.877

Gnomad4 ASJ AF: 0.949

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.906

Gnomad4 NFE AF: 0.913

Gnomad4 OTH AF: 0.903

Alfa AF: 0.911 Hom.: 47662

Bravo AF: 0.912

TwinsUK AF: 0.920 AC: 3412

ALSPAC AF: 0.913 AC: 3518

ESP6500AA AF: 0.948 AC: 4165

ESP6500EA AF: 0.917 AC: 7888

ExAC AF: 0.868 AC: 105388

Asia WGS AF: 0.686 AC: 2386 AN: 3478

EpiCase AF: 0.914

EpiControl AF: 0.917

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.25
DANN	Benign	0.55
DEOGEN2	Benign	0.0052	.;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.041	.;T;T
MetaRNN	Benign	7.3e-7	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N;N;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.32	N;N;N
REVEL	Benign	0.0040
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.0080	B;B;B
Vest4		0.015
MPC		0.18
ClinPred		0.0078	T
GERP RS		-7.8
Varity_R		0.024
gMVP		0.041

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs226891; hg19: chr16-19547747; COSMIC: COSV66816539; COSMIC: COSV66816539;