Genetic Variant NM_001378204.1:c.3843G>A (chr1-93264859-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

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

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.176).

BP6

Variant 1-93264859-G-A is Benign according to our data. Variant chr1-93264859-G-A is described in ClinVar as Benign. ClinVar VariationId is 3034057.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.878 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378204.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC18	NM_001378204.1	MANE Select	c.3843G>A	p.Arg1281Arg	synonymous	Exon 27 of 29	NP_001365133.1	A0A8I5KWA2
CCDC18	NM_001306076.1		c.3840G>A	p.Arg1280Arg	synonymous	Exon 27 of 29	NP_001293005.1	Q6PH87
CCDC18	NM_206886.4		c.3843G>A	p.Arg1281Arg	synonymous	Exon 27 of 28	NP_996769.3	Q6PH87

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC18	ENST00000690025.1	MANE Select	c.3843G>A	p.Arg1281Arg	synonymous	Exon 27 of 29	ENSP00000510597.1	A0A8I5KWA2
CCDC18	ENST00000401026.7	TSL:1	c.3843G>A	p.Arg1281Arg	synonymous	Exon 27 of 28	ENSP00000383808.3	E9PFB9
CCDC18	ENST00000447456.1	TSL:1	n.599G>A		non_coding_transcript_exon	Exon 4 of 4

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

GnomAD2 exomes

AF:

0.00563

AC:

1402

AN:

249006

AF XY:

0.00572

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 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

African (AFR)

AF:

0.00120

AC:

AN:

33454

American (AMR)

AF:

0.00300

AC:

134

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000268

AC:

AN:

26116

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39576

South Asian (SAS)

AF:

0.00335

AC:

289

AN:

86212

European-Finnish (FIN)

AF:

0.0124

AC:

661

AN:

53400

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00880

AC:

9783

AN:

1111456

Other (OTH)

AF:

0.00659

AC:

398

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

496

993

1489

1986

2482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.00536

AC:

816

AN:

152206

Hom.:

Cov.:

AF XY:

0.00504

AC XY:

375

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00197

AC:

AN:

41534

American (AMR)

AF:

0.00373

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.000771

AC:

AN:

5190

South Asian (SAS)

AF:

0.00332

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00945

AC:

100

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00801

AC:

545

AN:

68002

Other (OTH)

AF:

0.00522

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

130

173

216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00623

Hom.:

Bravo

AF:

0.00458

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00654

EpiControl

AF:

0.00688

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CCDC18-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.6

(source)

DANN

Benign

0.61

PhyloP100

0.88

Mutation Taster

=100/0

polymorphism

(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