rs750546126

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001378204.1(CCDC18):c.1318G>A(p.Val440Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CCDC18
NM_001378204.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.35

Publications

1 publications found

Variant links:

Genes affected

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

CCDC18 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06311756).

BP6

Variant 1-93210910-G-A is Benign according to our data. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-93210910-G-A is described in CliVar as Likely_benign. Clinvar id is 2264411.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC18	NM_001378204.1 link	c.1318G>A	p.Val440Met	missense_variant	Exon 10 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.1318G>A	p.Val440Met	missense_variant	Exon 10 of 29		NM_001378204.1	ENSP00000510597.1		A0A8I5KWA2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461490

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727054

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.00

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111802

Other (OTH)

AF:

0.00

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41406

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 03, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

3.6

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.020

T;.;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.063

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.57

N;.;.

PhyloP100

-1.4

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.26

N;N;N

REVEL

Benign

0.053

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.0050

B;.;.

Vest4

0.13

MutPred

0.26

Gain of ubiquitination at K438 (P = 0.0954);Gain of ubiquitination at K438 (P = 0.0954);.;

MVP

0.040

ClinPred

0.066

GERP RS

-6.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.045

gMVP

0.15

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over