Variant rs1061159 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.254C>T(p.Thr85Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,613,806 control chromosomes in the GnomAD database, including 42,652 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 0.25 ( 5005 hom., cov: 33)

Exomes 𝑓: 0.22 ( 37647 hom. )

Consequence

CCDC186
NM_018017.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.677

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:

CCDC186 (HGNC:):

CCDC186 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036338568).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC186	NM_018017.4 linkuse as main transcript	c.254C>T	p.Thr85Ile	missense_variant	2/16	ENST00000369287.8	NP_060487.2	Q7Z3E2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC186	ENST00000369287.8 linkuse as main transcript	c.254C>T	p.Thr85Ile	missense_variant	2/16	1	NM_018017.4	ENSP00000358293.3	Q7Z3E2
CCDC186	ENST00000369286.1 linkuse as main transcript	c.254C>T	p.Thr85Ile	missense_variant	2/2	1		ENSP00000358292.1	A0A0C4DFU7
CCDC186	ENST00000648613.1 linkuse as main transcript	c.254C>T	p.Thr85Ile	missense_variant	3/17			ENSP00000498136.1	Q7Z3E2
CCDC186	ENST00000369285.7 linkuse as main transcript	c.254C>T	p.Thr85Ile	missense_variant	3/3	2		ENSP00000358291.3	A0A0C4DFU7

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37719

AN:

152008

Hom.:

4987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.320

Gnomad EAS

AF:

0.0689

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.241

GnomAD3 exomes

AF:

0.204

AC:

51311

AN:

251098

Hom.:

5840

AF XY:

0.201

AC XY:

27330

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.324

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.316

Gnomad EAS exome

AF:

0.0689

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.230

Gnomad OTH exome

AF:

0.233

GnomAD4 exome

AF:

0.223

AC:

325317

AN:

1461680

Hom.:

37647

Cov.:

AF XY:

0.220

AC XY:

159781

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.324

Gnomad4 AMR exome

AF:

0.169

Gnomad4 ASJ exome

AF:

0.320

Gnomad4 EAS exome

AF:

0.0678

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.205

Gnomad4 NFE exome

AF:

0.231

Gnomad4 OTH exome

AF:

0.233

GnomAD4 genome

AF:

0.248

AC:

37786

AN:

152126

Hom.:

5005

Cov.:

AF XY:

0.245

AC XY:

18203

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.326

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.320

Gnomad4 EAS

AF:

0.0692

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.200

Gnomad4 NFE

AF:

0.232

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.232

Hom.:

10547

Bravo

AF:

0.254

TwinsUK

AF:

0.225

AC:

836

ALSPAC

AF:

0.244

AC:

941

ESP6500AA

AF:

0.317

AC:

1395

ESP6500EA

AF:

0.235

AC:

2024

ExAC

AF:

0.206

AC:

24995

Asia WGS

AF:

0.137

AC:

478

AN:

3478

EpiCase

AF:

0.247

EpiControl

AF:

0.237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.072

DANN

Benign

0.17

DEOGEN2

Benign

0.028

T;T;.;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.11

.;T;.;T

MetaRNN

Benign

0.0036

T;T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.86

N;.;N;N

REVEL

Benign

0.15

Sift

Benign

0.42

T;.;T;T

Sift4G

Benign

0.14

T;.;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.027

MPC

0.29

ClinPred

0.0080

GERP RS

-9.5

Varity_R

0.024

gMVP

0.063

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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