Variant 1-93207166-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001378204.1(CCDC18):c.977A>C(p.Asn326Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 1,601,230 control chromosomes in the GnomAD database, including 536,019 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.71 ( 41846 hom., cov: 32)

Exomes 𝑓: 0.82 ( 494173 hom. )

Consequence

CCDC18
NM_001378204.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.77

Variant links:

Genes affected

CCDC18 (HGNC:30370): (coiled-coil domain containing 18)

CCDC18 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.9724504E-7).

BP6

Variant 1-93207166-A-C is Benign according to our data. Variant chr1-93207166-A-C is described in ClinVar as [Benign]. Clinvar id is 3060557.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC18	NM_001378204.1 linkuse as main transcript	c.977A>C	p.Asn326Thr	missense_variant	9/29	ENST00000690025.1	NP_001365133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC18	ENST00000690025.1 linkuse as main transcript	c.977A>C	p.Asn326Thr	missense_variant	9/29		NM_001378204.1	ENSP00000510597	P4

Frequencies

GnomAD3 genomes

AF:

0.713

AC:

108288

AN:

151848

Hom.:

41829

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.790

Gnomad AMR

AF:

0.837

Gnomad ASJ

AF:

0.809

Gnomad EAS

AF:

0.960

Gnomad SAS

AF:

0.952

Gnomad FIN

AF:

0.852

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.816

Gnomad OTH

AF:

0.765

GnomAD3 exomes

AF:

0.833

AC:

205906

AN:

247058

Hom.:

87930

AF XY:

0.844

AC XY:

113147

AN XY:

134130

show subpopulations

Gnomad AFR exome

AF:

0.384

Gnomad AMR exome

AF:

0.901

Gnomad ASJ exome

AF:

0.803

Gnomad EAS exome

AF:

0.962

Gnomad SAS exome

AF:

0.954

Gnomad FIN exome

AF:

0.847

Gnomad NFE exome

AF:

0.821

Gnomad OTH exome

AF:

0.838

GnomAD4 exome

AF:

0.821

AC:

1190325

AN:

1449264

Hom.:

494173

Cov.:

AF XY:

0.827

AC XY:

596318

AN XY:

721360

show subpopulations

Gnomad4 AFR exome

AF:

0.371

Gnomad4 AMR exome

AF:

0.891

Gnomad4 ASJ exome

AF:

0.806

Gnomad4 EAS exome

AF:

0.959

Gnomad4 SAS exome

AF:

0.952

Gnomad4 FIN exome

AF:

0.843

Gnomad4 NFE exome

AF:

0.817

Gnomad4 OTH exome

AF:

0.807

GnomAD4 genome

AF:

0.713

AC:

108345

AN:

151966

Hom.:

41846

Cov.:

AF XY:

0.721

AC XY:

53545

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.391

Gnomad4 AMR

AF:

0.837

Gnomad4 ASJ

AF:

0.809

Gnomad4 EAS

AF:

0.960

Gnomad4 SAS

AF:

0.952

Gnomad4 FIN

AF:

0.852

Gnomad4 NFE

AF:

0.816

Gnomad4 OTH

AF:

0.763

Alfa

AF:

0.789

Hom.:

44106

Bravo

AF:

0.698

TwinsUK

AF:

0.807

AC:

2992

ALSPAC

AF:

0.807

AC:

3111

ESP6500AA

AF:

0.423

AC:

1547

ESP6500EA

AF:

0.822

AC:

6700

ExAC

AF:

0.823

AC:

99368

Asia WGS

AF:

0.901

AC:

3131

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CCDC18-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.;T

Eigen

Benign

0.0023

Eigen_PC

Benign

0.086

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

T;T;T

MetaRNN

Benign

8.0e-7

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;.;.

MutationTaster

Benign

0.079

P;P;P;P

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.078

Sift

Benign

0.58

T;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.42

B;.;.

Vest4

0.16

ClinPred

0.020

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.097

gMVP

0.17

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over