Genetic Variant CCDC18:p.Arg1281Arg (chr1-93264859-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001378204.1(CCDC18):c.3843G>A(p.Arg1281Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00753 in 1,613,256 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0054 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 54 hom. )

Consequence

CCDC18
NM_001378204.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.878

Variant links:

Genes affected

CCDC18 (HGNC:30370): (coiled-coil domain containing 18)

CCDC18 links:

CCDC18-AS1 (HGNC:52262): (CCDC18 antisense RNA 1)

CCDC18-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 1-93264859-G-A is Benign according to our data. Variant chr1-93264859-G-A is described in ClinVar as [Benign]. Clinvar id is 3034057.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-93264859-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.878 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC18	NM_001378204.1 link	c.3843G>A	p.Arg1281Arg	synonymous_variant	Exon 27 of 29	ENST00000690025.1	NP_001365133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC18	ENST00000690025.1 link	c.3843G>A	p.Arg1281Arg	synonymous_variant	Exon 27 of 29		NM_001378204.1	ENSP00000510597.1		A0A8I5KWA2

Frequencies

GnomAD3 genomes

AF:

0.00536

AC:

815

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00801

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00563

AC:

1402

AN:

249006

Hom.:

AF XY:

0.00572

AC XY:

773

AN XY:

135102

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.00293

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00350

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.00798

Gnomad OTH exome

AF:

0.00745

GnomAD4 exome

AF:

0.00775

AC:

11329

AN:

1461050

Hom.:

Cov.:

AF XY:

0.00760

AC XY:

5523

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00335

Gnomad4 FIN exome

AF:

0.0124

Gnomad4 NFE exome

AF:

0.00880

Gnomad4 OTH exome

AF:

0.00659

GnomAD4 genome

AF:

0.00536

AC:

816

AN:

152206

Hom.:

Cov.:

AF XY:

0.00504

AC XY:

375

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00197

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00945

Gnomad4 NFE

AF:

0.00801

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00623

Hom.:

Bravo

AF:

0.00458

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00654

EpiControl

AF:

0.00688

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CCDC18-related disorder

Benign:1

Apr 11, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.6

DANN

Benign

0.61

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over