Genetic Variant CCDC184:p.Glu140Asp (chr12-48184542-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001013635.4(CCDC184):c.420A>C(p.Glu140Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 1,553,894 control chromosomes in the GnomAD database, including 429,862 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.70 ( 37679 hom., cov: 29)

Exomes 𝑓: 0.74 ( 392183 hom. )

Consequence

CCDC184
NM_001013635.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

Publications

23 publications found

Variant links:

Genes affected

CCDC184 (HGNC:33749): (coiled-coil domain containing 184) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CCDC184 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.957121E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC184	NM_001013635.4 link	c.420A>C	p.Glu140Asp	missense_variant	Exon 1 of 1	ENST00000316554.5	NP_001013657.3	Q52MB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC184	ENST00000316554.5 link	c.420A>C	p.Glu140Asp	missense_variant	Exon 1 of 1	6	NM_001013635.4	ENSP00000320849.3		Q52MB2

Frequencies

GnomAD3 genomes

AF:

0.698

AC:

105940

AN:

151700

Hom.:

37649

Cov.:

show subpopulations

Gnomad AFR

AF:

0.643

Gnomad AMI

AF:

0.784

Gnomad AMR

AF:

0.595

Gnomad ASJ

AF:

0.811

Gnomad EAS

AF:

0.406

Gnomad SAS

AF:

0.653

Gnomad FIN

AF:

0.715

Gnomad MID

AF:

0.845

Gnomad NFE

AF:

0.770

Gnomad OTH

AF:

0.722

GnomAD2 exomes

AF:

0.669

AC:

105186

AN:

157124

AF XY:

0.681

show subpopulations

Gnomad AFR exome

AF:

0.645

Gnomad AMR exome

AF:

0.469

Gnomad ASJ exome

AF:

0.800

Gnomad EAS exome

AF:

0.415

Gnomad FIN exome

AF:

0.701

Gnomad NFE exome

AF:

0.772

Gnomad OTH exome

AF:

0.718

GnomAD4 exome

AF:

0.743

AC:

1041905

AN:

1402076

Hom.:

392183

Cov.:

AF XY:

0.743

AC XY:

514812

AN XY:

693110

show subpopulations

African (AFR)

AF:

0.643

AC:

20756

AN:

32284

American (AMR)

AF:

0.486

AC:

17779

AN:

36608

Ashkenazi Jewish (ASJ)

AF:

0.801

AC:

20233

AN:

25248

East Asian (EAS)

AF:

0.415

AC:

15322

AN:

36924

South Asian (SAS)

AF:

0.676

AC:

54464

AN:

80594

European-Finnish (FIN)

AF:

0.709

AC:

28546

AN:

40264

Middle Eastern (MID)

AF:

0.826

AC:

4701

AN:

5690

European-Non Finnish (NFE)

AF:

0.771

AC:

837665

AN:

1085992

Other (OTH)

AF:

0.726

AC:

42439

AN:

58472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

16715

33429

50144

66858

83573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.698

AC:

106015

AN:

151818

Hom.:

37679

Cov.:

AF XY:

0.692

AC XY:

51309

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.643

AC:

26624

AN:

41410

American (AMR)

AF:

0.595

AC:

9084

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.811

AC:

2813

AN:

3468

East Asian (EAS)

AF:

0.407

AC:

2068

AN:

5086

South Asian (SAS)

AF:

0.653

AC:

3139

AN:

4806

European-Finnish (FIN)

AF:

0.715

AC:

7541

AN:

10554

Middle Eastern (MID)

AF:

0.844

AC:

248

AN:

294

European-Non Finnish (NFE)

AF:

0.770

AC:

52275

AN:

67914

Other (OTH)

AF:

0.717

AC:

1510

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1565

3130

4695

6260

7825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.743

Hom.:

94783

Bravo

AF:

0.686

TwinsUK

AF:

0.770

AC:

2854

ALSPAC

AF:

0.761

AC:

2931

ESP6500AA

AF:

0.668

AC:

2887

ESP6500EA

AF:

0.785

AC:

6639

ExAC

AF:

0.626

AC:

68884

Asia WGS

AF:

0.537

AC:

1871

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.3

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.17

MetaRNN

Benign

9.0e-7

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.34

PhyloP100

-1.1

PROVEAN

Benign

0.80

REVEL

Benign

0.032

Sift

Benign

1.0

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.033

MutPred

0.084

Loss of helix (P = 0.0444);

MPC

0.34

ClinPred

0.0012

GERP RS

-1.7

Varity_R

0.049

gMVP

0.024

Mutation Taster

=100/0

polymorphism (auto)

(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.

chr12-48184542-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over