Variant chr18-32974611-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001105528.4(CCDC178):c.2459A>G(p.Gln820Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000183 in 1,613,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

CCDC178
NM_001105528.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.201

Variant links:

Genes affected

CCDC178 (HGNC:29588): (coiled-coil domain containing 178) Located in ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

CCDC178 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.003311932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC178	NM_001105528.4 linkuse as main transcript	c.2459A>G	p.Gln820Arg	missense_variant	22/23	ENST00000383096.8	NP_001098998.1	Q5BJE1-1A1L4G8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC178	ENST00000383096.8 linkuse as main transcript	c.2459A>G	p.Gln820Arg	missense_variant	22/23	5	NM_001105528.4	ENSP00000372576.3		Q5BJE1-1

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000303

AC:

AN:

250990

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00536

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000184

AC:

269

AN:

1461166

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

140

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00662

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000495

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.000177

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000343

Hom.:

Bravo

AF:

0.000185

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2023

The c.2459A>G (p.Q820R) alteration is located in exon 21 (coding exon 20) of the CCDC178 gene. This alteration results from a A to G substitution at nucleotide position 2459, causing the glutamine (Q) at amino acid position 820 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.010

.;T;.;T;.;.;.;.;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.67

T;T;T;.;T;T;T;.;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0033

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N;.;N;.;.;.;.;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.2

.;N;.;N;N;.;N;.;.

REVEL

Benign

0.028

Sift

Benign

0.28

.;T;.;T;T;.;T;.;.

Sift4G

Uncertain

0.053

T;T;T;T;T;D;T;T;T

Polyphen

0.023

.;B;.;B;B;.;B;B;.

Vest4

0.25

MVP

0.12

MPC

0.019

ClinPred

0.0072

GERP RS

0.10

Varity_R

0.11

gMVP

0.20

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