NM_018017.4:c.-193G>A

Variant names:

• chr10-114174146-C-T
• rs17091403
• NM_018017.4:c.-193G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 26 publications found

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]

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]

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC186	NM_018017.4	c.-193G>A		5_prime_UTR_variant	Exon 1 of 16	ENST00000369287.8	NP_060487.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC186	ENST00000369287.8	c.-193G>A		5_prime_UTR_variant	Exon 1 of 16	1	NM_018017.4	ENSP00000358293.3

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11437 AN: 152220 Hom.: 514 Cov.: 33

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

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.: 0 AF XY: 0.0755 AC XY: 13567 AN XY: 179766

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: 0 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: 61 AN: 2762

European-Non Finnish (NFE) AF: 0.103 AC: 16279 AN: 158156

Other (OTH) AF: 0.0724 AC: 1032 AN: 14250

GnomAD4 genome AF: 0.0750 AC: 11432 AN: 152338 Hom.: 514 Cov.: 33 AF XY: 0.0731 AC XY: 5446 AN XY: 74500

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: 2 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: 24 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6917 AN: 68016

Other (OTH) AF: 0.0605 AC: 128 AN: 2116

Alfa AF: 0.0833 Hom.: 709

Bravo AF: 0.0665

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.8
DANN	Benign	0.73
PhyloP100		-0.16
PromoterAI		-0.0013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17091403; hg19: chr10-115933905; COSMIC: COSV65159459;