chr16-19537418-A-G

Variant names:

• chr16-19537418-A-G
• rs17227190
• NM_001323572.2:c.1749A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001323572.2(CCP110):​c.1749A>G​(p.Lys583Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0736 in 1,613,200 control chromosomes in the GnomAD database, including 4,737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (360 hom., cov: 33)
  • Exomes 𝑓: 0.075 (4377 hom.)
• Consequence: CCP110 NM_001323572.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.57
• Publications: 11 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 16-19537418-A-G is Benign according to our data. Variant chr16-19537418-A-G is described in ClinVar as [Benign]. Clinvar id is 402515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.58 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCP110	NM_001323572.2	c.1749A>G	p.Lys583Lys	synonymous_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.1749A>G	p.Lys583Lys	synonymous_variant	Exon 4 of 14		NM_001323572.2	ENSP00000511625.1

Frequencies

GnomAD3 genomes AF: 0.0629 AC: 9570 AN: 152198 Hom.: 357 Cov.: 33

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0949

Gnomad FIN AF: 0.0873

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0728

Gnomad OTH AF: 0.0602

GnomAD2 exomes AF: 0.0819 AC: 20543 AN: 250780 AF XY: 0.0811

Gnomad AFR exome AF: 0.0153

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.0338

Gnomad EAS exome AF: 0.129

Gnomad FIN exome AF: 0.0936

Gnomad NFE exome AF: 0.0712

Gnomad OTH exome AF: 0.0867

GnomAD4 exome AF: 0.0747 AC: 109174 AN: 1460884 Hom.: 4377 Cov.: 32 AF XY: 0.0753 AC XY: 54721 AN XY: 726720

African (AFR) AF: 0.0133 AC: 444 AN: 33424

American (AMR) AF: 0.122 AC: 5454 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 888 AN: 26122

East Asian (EAS) AF: 0.119 AC: 4730 AN: 39696

South Asian (SAS) AF: 0.0881 AC: 7585 AN: 86094

European-Finnish (FIN) AF: 0.0930 AC: 4965 AN: 53410

Middle Eastern (MID) AF: 0.0673 AC: 388 AN: 5764

European-Non Finnish (NFE) AF: 0.0722 AC: 80209 AN: 1111394

Other (OTH) AF: 0.0747 AC: 4511 AN: 60366

GnomAD4 genome AF: 0.0628 AC: 9573 AN: 152316 Hom.: 360 Cov.: 33 AF XY: 0.0639 AC XY: 4757 AN XY: 74482

African (AFR) AF: 0.0178 AC: 740 AN: 41576

American (AMR) AF: 0.100 AC: 1536 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3472

East Asian (EAS) AF: 0.133 AC: 689 AN: 5190

South Asian (SAS) AF: 0.0948 AC: 457 AN: 4822

European-Finnish (FIN) AF: 0.0873 AC: 927 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0728 AC: 4953 AN: 68028

Other (OTH) AF: 0.0591 AC: 125 AN: 2114

Alfa AF: 0.0562 Hom.: 175

Bravo AF: 0.0632

Asia WGS AF: 0.110 AC: 382 AN: 3478

EpiCase AF: 0.0688

EpiControl AF: 0.0672

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
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.6
DANN	Benign	0.66
PhyloP100		1.6
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: rs17227190; hg19: chr16-19548740; COSMIC: COSV66817039; COSMIC: COSV66817039;