Genetic Variant CCDC18:p.Lys1440delinsAsnLeu (chr1-93270780-A-ACCT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PM4_SupportingBP6

The NM_001378204.1(CCDC18):c.4319_4320insCCT(p.Lys1440delinsAsnLeu) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00043 in 1,545,196 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00072 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 0 hom. )

Consequence

CCDC18
NM_001378204.1 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.926

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001378204.1. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 1-93270780-A-ACCT is Benign according to our data. Variant chr1-93270780-A-ACCT is described in ClinVar as Likely_benign. ClinVar VariationId is 3047544.Status of the report is no_assertion_criteria_provided, 0 stars.

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.4319_4320insCCT	p.Lys1440delinsAsnLeu	disruptive_inframe_insertion	Exon 28 of 29	NP_001365133.1	A0A8I5KWA2
CCDC18	NM_001306076.1		c.4316_4317insCCT	p.Lys1439delinsAsnLeu	disruptive_inframe_insertion	Exon 28 of 29	NP_001293005.1	Q6PH87
CCDC18	NM_206886.4		c.3885+5879_3885+5880insCCT		intron	N/A	NP_996769.3	Q6PH87

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC18	ENST00000690025.1	MANE Select	c.4319_4320insCCT	p.Lys1440delinsAsnLeu	disruptive_inframe_insertion	Exon 28 of 29	ENSP00000510597.1	A0A8I5KWA2
CCDC18	ENST00000401026.7	TSL:1	c.3885+5879_3885+5880insCCT		intron	N/A	ENSP00000383808.3	E9PFB9
CCDC18	ENST00000935053.1		c.4319_4320insCCT	p.Lys1440delinsAsnLeu	disruptive_inframe_insertion	Exon 28 of 29	ENSP00000605112.1

Frequencies

GnomAD3 genomes

AF:

0.000716

AC:

109

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000610

AC:

AN:

144208

AF XY:

0.000527

show subpopulations

Gnomad AFR exome

AF:

0.000300

Gnomad AMR exome

AF:

0.00238

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000601

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.00171

GnomAD4 exome

AF:

0.000399

AC:

556

AN:

1392848

Hom.:

Cov.:

AF XY:

0.000386

AC XY:

265

AN XY:

687040

show subpopulations

African (AFR)

AF:

0.0000643

AC:

AN:

31116

American (AMR)

AF:

0.00219

AC:

AN:

34276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24866

East Asian (EAS)

AF:

0.00

AC:

AN:

35650

South Asian (SAS)

AF:

0.00

AC:

AN:

78552

European-Finnish (FIN)

AF:

0.0000208

AC:

AN:

48078

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5498

European-Non Finnish (NFE)

AF:

0.000428

AC:

461

AN:

1077148

Other (OTH)

AF:

0.000295

AC:

AN:

57664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000715

AC:

109

AN:

152348

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41588

American (AMR)

AF:

0.00457

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

68018

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000391

Hom.:

Bravo

AF:

0.000616

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Likely 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

PhyloP100

-0.93

Splicing

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