Variant rs12782946 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018017.4(CCDC186):c.536G>A(p.Arg179Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0733 in 1,613,686 control chromosomes in the GnomAD database, including 4,984 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.057 ( 339 hom., cov: 33)

Exomes 𝑓: 0.075 ( 4645 hom. )

Consequence

CCDC186
NM_018017.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.428

Variant links:

Genes affected

CCDC186 (HGNC:24349): (coiled-coil domain containing 186) Predicted to enable small GTPase binding activity. Predicted to be involved in vesicle cytoskeletal trafficking. Predicted to act upstream of or within insulin secretion involved in cellular response to glucose stimulus and response to bacterium. Predicted to be located in Golgi apparatus. Predicted to be active in trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

CCDC186 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013920665).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC186	NM_018017.4 linkuse as main transcript	c.536G>A	p.Arg179Gln	missense_variant	2/16	ENST00000369287.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CCDC186	ENST00000369287.8 linkuse as main transcript	c.536G>A	p.Arg179Gln	missense_variant	2/16	1	NM_018017.4	P1
CCDC186	ENST00000369286.1 linkuse as main transcript	c.536G>A	p.Arg179Gln	missense_variant	2/2	1
CCDC186	ENST00000648613.1 linkuse as main transcript	c.536G>A	p.Arg179Gln	missense_variant	3/17			P1
CCDC186	ENST00000369285.7 linkuse as main transcript	c.536G>A	p.Arg179Gln	missense_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0571

AC:

8689

AN:

152074

Hom.:

339

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.0769

Gnomad AMR

AF:

0.0713

Gnomad ASJ

AF:

0.0741

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.0817

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0815

Gnomad OTH

AF:

0.0672

GnomAD3 exomes

AF:

0.0555

AC:

13923

AN:

251008

Hom.:

526

AF XY:

0.0552

AC XY:

7496

AN XY:

135688

show subpopulations

Gnomad AFR exome

AF:

0.0166

Gnomad AMR exome

AF:

0.0459

Gnomad ASJ exome

AF:

0.0708

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00893

Gnomad FIN exome

AF:

0.0715

Gnomad NFE exome

AF:

0.0801

Gnomad OTH exome

AF:

0.0721

GnomAD4 exome

AF:

0.0750

AC:

109643

AN:

1461494

Hom.:

4645

Cov.:

AF XY:

0.0731

AC XY:

53166

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.0149

Gnomad4 AMR exome

AF:

0.0476

Gnomad4 ASJ exome

AF:

0.0730

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00848

Gnomad4 FIN exome

AF:

0.0746

Gnomad4 NFE exome

AF:

0.0864

Gnomad4 OTH exome

AF:

0.0680

GnomAD4 genome

AF:

0.0571

AC:

8689

AN:

152192

Hom.:

339

Cov.:

AF XY:

0.0559

AC XY:

4158

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0160

Gnomad4 AMR

AF:

0.0712

Gnomad4 ASJ

AF:

0.0741

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00766

Gnomad4 FIN

AF:

0.0817

Gnomad4 NFE

AF:

0.0815

Gnomad4 OTH

AF:

0.0665

Alfa

AF:

0.0777

Hom.:

1291

Bravo

AF:

0.0562

TwinsUK

AF:

0.0903

AC:

335

ALSPAC

AF:

0.0929

AC:

358

ESP6500AA

AF:

0.0209

AC:

ESP6500EA

AF:

0.0826

AC:

710

ExAC

AF:

0.0535

AC:

6493

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.0904

EpiControl

AF:

0.0855

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.76

Cadd

Benign

9.6

Dann

Uncertain

0.99

DEOGEN2

Benign

0.025

T;T;.;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.077

MetaRNN

Benign

0.0014

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

P;P;P

PROVEAN

Benign

-0.060

N;.;N;N

REVEL

Benign

0.12

Sift

Benign

0.67

T;.;T;T

Sift4G

Benign

0.58

T;.;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.073

MPC

0.31

ClinPred

0.011

GERP RS

-1.3

Varity_R

0.018

gMVP

0.16

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over