rs17091403

Variant names:

Variant summary

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

The NM_018017.4(CCDC186):c.-193G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 470,688 control chromosomes in the GnomAD database, including 1,737 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 0.075 ( 514 hom., cov: 33)

Exomes 𝑓: 0.078 ( 1223 hom. )

Consequence

CCDC186
NM_018017.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.161

Publications

26 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:

MIR2110 (HGNC:37071): (microRNA 2110) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR2110 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (REVEL=0.016).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0997 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	UniProt
CCDC186	NM_018017.4	MANE Select	c.-193G>A	5_prime_UTR	Exon 1 of 16	NP_060487.2
CCDC186	NM_001321829.1		c.-318G>A	5_prime_UTR	Exon 1 of 17	NP_001308758.1	Q7Z3E2
CCDC186	NM_153249.1		c.-318G>A	5_prime_UTR	Exon 1 of 3	NP_694981.1	Q7Z3E2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC186	ENST00000369287.8	TSL:1 MANE Select	c.-193G>A	5_prime_UTR	Exon 1 of 16	ENSP00000358293.3	Q7Z3E2
CCDC186	ENST00000369286.1	TSL:1	c.-193G>A	5_prime_UTR	Exon 1 of 2	ENSP00000358292.1	A0A0C4DFU7
CCDC186	ENST00000648613.1		c.-318G>A	5_prime_UTR	Exon 1 of 17	ENSP00000498136.1	Q7Z3E2

Frequencies

GnomAD3 genomes

AF:

0.0751

AC:

11437

AN:

152220

Hom.:

514

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0501

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.0445

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0389

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.0616

GnomAD2 exomes

AF:

0.0667

AC:

10136

AN:

152078

AF XY:

0.0666

show subpopulations

Gnomad AFR exome

AF:

0.0510

Gnomad AMR exome

AF:

0.0346

Gnomad ASJ exome

AF:

0.0400

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.0977

Gnomad OTH exome

AF:

0.0617

GnomAD4 exome

AF:

0.0779

AC:

24811

AN:

318350

Hom.:

1223

Cov.:

AF XY:

0.0755

AC XY:

13567

AN XY:

179766

show subpopulations

African (AFR)

AF:

0.0518

AC:

446

AN:

8616

American (AMR)

AF:

0.0349

AC:

945

AN:

27098

Ashkenazi Jewish (ASJ)

AF:

0.0400

AC:

425

AN:

10624

East Asian (EAS)

AF:

0.00

AC:

AN:

9188

South Asian (SAS)

AF:

0.0418

AC:

2488

AN:

59592

European-Finnish (FIN)

AF:

0.112

AC:

3135

AN:

28064

Middle Eastern (MID)

AF:

0.0221

AC:

AN:

2762

European-Non Finnish (NFE)

AF:

0.103

AC:

16279

AN:

158156

Other (OTH)

AF:

0.0724

AC:

1032

AN:

14250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1284

2567

3851

5134

6418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.0750

AC:

11432

AN:

152338

Hom.:

514

Cov.:

AF XY:

0.0731

AC XY:

5446

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0499

AC:

2077

AN:

41584

American (AMR)

AF:

0.0444

AC:

680

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

142

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0383

AC:

185

AN:

4832

European-Finnish (FIN)

AF:

0.110

AC:

1167

AN:

10618

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6917

AN:

68016

Other (OTH)

AF:

0.0605

AC:

128

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

559

1118

1678

2237

2796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0833

Hom.:

709

Bravo

AF:

0.0665

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

3.8

(source)

DANN

Benign

0.73

PhyloP100

-0.16

PromoterAI

-0.0013

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

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