Variant 18-33092876-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001105528.4(CCDC178):c.2273G>T(p.Arg758Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,568,174 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 10 hom. )

Consequence

CCDC178
NM_001105528.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.820

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011208296).

BP6

Variant 18-33092876-C-A is Benign according to our data. Variant chr18-33092876-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648634.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC178	NM_001105528.4 linkuse as main transcript	c.2273G>T	p.Arg758Leu	missense_variant	21/23	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.2273G>T	p.Arg758Leu	missense_variant	21/23	5	NM_001105528.4	ENSP00000372576.3		Q5BJE1-1

Frequencies

GnomAD3 genomes

AF:

0.00261

AC:

397

AN:

151872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00664

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00352

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00323

AC:

709

AN:

219380

Hom.:

AF XY:

0.00339

AC XY:

405

AN XY:

119588

show subpopulations

Gnomad AFR exome

AF:

0.000821

Gnomad AMR exome

AF:

0.000728

Gnomad ASJ exome

AF:

0.00287

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00266

Gnomad FIN exome

AF:

0.00642

Gnomad NFE exome

AF:

0.00418

Gnomad OTH exome

AF:

0.00308

GnomAD4 exome

AF:

0.00334

AC:

4735

AN:

1416184

Hom.:

Cov.:

AF XY:

0.00327

AC XY:

2303

AN XY:

705262

show subpopulations

Gnomad4 AFR exome

AF:

0.000484

Gnomad4 AMR exome

AF:

0.000654

Gnomad4 ASJ exome

AF:

0.00312

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.00296

Gnomad4 FIN exome

AF:

0.00620

Gnomad4 NFE exome

AF:

0.00354

Gnomad4 OTH exome

AF:

0.00327

GnomAD4 genome

AF:

0.00261

AC:

397

AN:

151990

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

202

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00664

Gnomad4 NFE

AF:

0.00352

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00382

Hom.:

Bravo

AF:

0.00233

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00210

AC:

ExAC

AF:

0.00351

AC:

426

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

CCDC178: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.3

DANN

Benign

0.84

DEOGEN2

Benign

0.031

T;T;.;.;.;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.79

T;.;T;T;.;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.011

T;T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.0

L;L;.;.;.;L

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.9

D;D;D;D;.;.

REVEL

Benign

0.14

Sift

Uncertain

0.0040

D;D;D;D;.;.

Sift4G

Uncertain

0.057

T;T;T;D;D;T

Polyphen

1.0

D;D;D;D;D;.

Vest4

0.40

MVP

0.26

MPC

0.12

ClinPred

0.038

GERP RS

3.0

Varity_R

0.15

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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