rs10783231

chr12-48184542-A-Cchr12-48184542-A-Gchr12-48184542-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.70 (37679 hom., cov: 29)
  • Exomes 𝑓: 0.74 (392183 hom.)
• Consequence: CCDC184 NM_001013635.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CCDC184	NM_001013635.4	c.420A>C	p.Glu140Asp	missense_variant	1/1	ENST00000316554.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC184	ENST00000316554.5	c.420A>C	p.Glu140Asp	missense_variant	1/1		NM_001013635.4	P1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 105940 AN: 151700 Hom.: 37649 Cov.: 29

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

GnomAD3 exomes AF: 0.669 AC: 105186 AN: 157124 Hom.: 36689 AF XY: 0.681 AC XY: 58249 AN XY: 85578

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 SAS exome AF: 0.676

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.: 74 AF XY: 0.743 AC XY: 514812 AN XY: 693110

Gnomad4 AFR exome AF: 0.643

Gnomad4 AMR exome AF: 0.486

Gnomad4 ASJ exome AF: 0.801

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.676

Gnomad4 FIN exome AF: 0.709

Gnomad4 NFE exome AF: 0.771

Gnomad4 OTH exome AF: 0.726

GnomAD4 genome AF: 0.698 AC: 106015 AN: 151818 Hom.: 37679 Cov.: 29 AF XY: 0.692 AC XY: 51309 AN XY: 74156

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.811

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.717

Alfa AF: 0.752 Hom.: 67995

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	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.3
Dann	Benign	0.54
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	9.0e-7	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.34	N
MutationTaster	Benign	1.0	P
PROVEAN	Benign	0.80	N
REVEL	Benign	0.032
Sift	Benign	1.0	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.033
MutPred		0.084		Loss of helix (P = 0.0444);
MPC		0.34
ClinPred		0.0012	T
GERP RS		-1.7
Varity_R		0.049
gMVP		0.024

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

LitVar

Other links and lift over

dbSNP: rs10783231; hg19: chr12-48578325; COSMIC: COSV57251551; COSMIC: COSV57251551;