Genetic Variant CCDC186:c.1513-145G>C (chr10-114135200-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018017.4(CCDC186):c.1513-145G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 785,710 control chromosomes in the GnomAD database, including 135,689 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.65 ( 33847 hom., cov: 31)

Exomes 𝑓: 0.56 ( 101842 hom. )

Consequence

CCDC186
NM_018017.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.475

Publications

3 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018017.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CCDC186	NM_018017.4	MANE Select	c.1513-145G>C	intron	N/A	NP_060487.2
CCDC186	NM_001321829.1		c.1513-145G>C	intron	N/A	NP_001308758.1
CCDC186	NR_135815.1		n.1905-145G>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CCDC186	ENST00000369287.8	TSL:1 MANE Select	c.1513-145G>C	intron	N/A	ENSP00000358293.3
CCDC186	ENST00000648613.1		c.1513-145G>C	intron	N/A	ENSP00000498136.1
CCDC186	ENST00000428953.1	TSL:2	c.397-145G>C	intron	N/A	ENSP00000415344.1

Frequencies

GnomAD3 genomes

AF:

0.647

AC:

98267

AN:

151834

Hom.:

33782

Cov.:

show subpopulations

Gnomad AFR

AF:

0.901

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.536

Gnomad EAS

AF:

0.375

Gnomad SAS

AF:

0.574

Gnomad FIN

AF:

0.519

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.590

GnomAD4 exome

AF:

0.559

AC:

354070

AN:

633758

Hom.:

101842

AF XY:

0.558

AC XY:

178147

AN XY:

319048

show subpopulations

African (AFR)

AF:

0.912

AC:

11773

AN:

12916

American (AMR)

AF:

0.547

AC:

4910

AN:

8974

Ashkenazi Jewish (ASJ)

AF:

0.540

AC:

7048

AN:

13062

East Asian (EAS)

AF:

0.357

AC:

8608

AN:

24114

South Asian (SAS)

AF:

0.583

AC:

18685

AN:

32074

European-Finnish (FIN)

AF:

0.532

AC:

14287

AN:

26868

Middle Eastern (MID)

AF:

0.543

AC:

1212

AN:

2230

European-Non Finnish (NFE)

AF:

0.559

AC:

270146

AN:

482838

Other (OTH)

AF:

0.567

AC:

17401

AN:

30682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

7215

14431

21646

28862

36077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5978

11956

17934

23912

29890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.648

AC:

98390

AN:

151952

Hom.:

33847

Cov.:

AF XY:

0.640

AC XY:

47512

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.902

AC:

37420

AN:

41506

American (AMR)

AF:

0.568

AC:

8674

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.536

AC:

1858

AN:

3466

East Asian (EAS)

AF:

0.376

AC:

1942

AN:

5166

South Asian (SAS)

AF:

0.573

AC:

2763

AN:

4820

European-Finnish (FIN)

AF:

0.519

AC:

5461

AN:

10522

Middle Eastern (MID)

AF:

0.629

AC:

185

AN:

294

European-Non Finnish (NFE)

AF:

0.564

AC:

38306

AN:

67904

Other (OTH)

AF:

0.591

AC:

1247

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1573

3145

4718

6290

7863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.471

Hom.:

1248

Bravo

AF:

0.660

Asia WGS

AF:

0.558

AC:

1935

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.55

(source)

DANN

Benign

0.26

PhyloP100

-0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over