rs7190666

Variant names:

• chr16-19536794-G-A
• rs7190666
• NM_001323572.2:c.1125G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-19536794-G-A
• chr16-19536794-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001323572.2(CCP110):​c.1125G>A​(p.Met375Ile) variant causes a missense change. The variant allele was found at a frequency of 0.15 in 1,613,874 control chromosomes in the GnomAD database, including 18,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1858 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16986 hom.)
• Consequence: CCP110 NM_001323572.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.39
• Publications: 25 publications found

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]

CCP110 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015616417).
• BP6: Variant 16-19536794-G-A is Benign according to our data. Variant chr16-19536794-G-A is described in ClinVar as Benign. ClinVar VariationId is 402513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCP110	NM_001323572.2	c.1125G>A	p.Met375Ile	missense_variant	Exon 4 of 14	ENST00000694978.1	NP_001310501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCP110	ENST00000694978.1	c.1125G>A	p.Met375Ile	missense_variant	Exon 4 of 14		NM_001323572.2	ENSP00000511625.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23341 AN: 152064 Hom.: 1859 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0950

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.172

GnomAD2 exomes AF: 0.148 AC: 37144 AN: 250300 AF XY: 0.144

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.192

Gnomad ASJ exome AF: 0.205

Gnomad EAS exome AF: 0.155

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.150 AC: 218810 AN: 1461694 Hom.: 16986 Cov.: 37 AF XY: 0.148 AC XY: 107581 AN XY: 727130

African (AFR) AF: 0.155 AC: 5200 AN: 33478

American (AMR) AF: 0.189 AC: 8447 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 5257 AN: 26132

East Asian (EAS) AF: 0.180 AC: 7136 AN: 39698

South Asian (SAS) AF: 0.0853 AC: 7354 AN: 86252

European-Finnish (FIN) AF: 0.115 AC: 6131 AN: 53390

Middle Eastern (MID) AF: 0.201 AC: 1162 AN: 5768

European-Non Finnish (NFE) AF: 0.152 AC: 168830 AN: 1111872

Other (OTH) AF: 0.154 AC: 9293 AN: 60390

GnomAD4 genome AF: 0.153 AC: 23344 AN: 152180 Hom.: 1858 Cov.: 32 AF XY: 0.153 AC XY: 11384 AN XY: 74408

African (AFR) AF: 0.157 AC: 6523 AN: 41508

American (AMR) AF: 0.196 AC: 2993 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 732 AN: 3470

East Asian (EAS) AF: 0.168 AC: 868 AN: 5172

South Asian (SAS) AF: 0.0944 AC: 456 AN: 4828

European-Finnish (FIN) AF: 0.114 AC: 1203 AN: 10586

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10059 AN: 68000

Other (OTH) AF: 0.169 AC: 357 AN: 2116

Alfa AF: 0.152 Hom.: 6211

Bravo AF: 0.163

TwinsUK AF: 0.150 AC: 557

ALSPAC AF: 0.145 AC: 558

ESP6500AA AF: 0.158 AC: 696

ESP6500EA AF: 0.156 AC: 1341

ExAC AF: 0.145 AC: 17594

Asia WGS AF: 0.126 AC: 440 AN: 3478

EpiCase AF: 0.153

EpiControl AF: 0.156

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0	.;T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.0	.;T;T
MetaRNN	Benign	0.0016	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M;M;M
PhyloP100		4.4
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.025	D;D;D
Vest4		0.26
ClinPred		0.022	T
GERP RS		4.0
Varity_R		0.76
gMVP		0.10
Mutation Taster		=97/3	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: rs7190666; hg19: chr16-19548116; COSMIC: COSV66816649; COSMIC: COSV66816649;