Genetic Variant NM_031455.4:c.*1455G>A (chr10-12896961-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_031455.4(CCDC3):c.*1455G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,258 control chromosomes in the GnomAD database, including 4,249 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 4238 hom., cov: 32)

Exomes 𝑓: 0.32 ( 11 hom. )

Consequence

CCDC3
NM_031455.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00300

Publications

9 publications found

Variant links:

Genes affected

CCDC3 (HGNC:23813): (coiled-coil domain containing 3) Involved in negative regulation of gene expression; negative regulation of lipid metabolic process; and negative regulation of tumor necrosis factor-mediated signaling pathway. Located in endoplasmic reticulum and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

CCDC3 links:

ENSG00000285520 (HGNC:):

ENSG00000285520 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC3	NM_031455.4 link	c.*1455G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000378825.5	NP_113643.1	Q9BQI4-1
CCDC3	NM_001282658.2 link	c.*1455G>A		3_prime_UTR_variant	Exon 7 of 7		NP_001269587.1	Q9BQI4-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC3	ENST00000378825.5 link	c.*1455G>A	3_prime_UTR_variant	Exon 3 of 3	1	NM_031455.4	ENSP00000368102.3	Q9BQI4-1
CCDC3	ENST00000378839.1 link	c.*1455G>A	3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000368116.1	Q9BQI4-2
ENSG00000285520	ENST00000649832.1 link	n.511-1551C>T	intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32362

AN:

151964

Hom.:

4242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0625

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.225

GnomAD4 exome

AF:

0.324

AC:

AN:

176

Hom.:

Cov.:

AF XY:

0.319

AC XY:

AN XY:

144

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.346

AC:

AN:

162

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.213

AC:

32346

AN:

152082

Hom.:

4238

Cov.:

AF XY:

0.210

AC XY:

15587

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0624

AC:

2590

AN:

41516

American (AMR)

AF:

0.194

AC:

2969

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

1294

AN:

3464

East Asian (EAS)

AF:

0.220

AC:

1135

AN:

5164

South Asian (SAS)

AF:

0.136

AC:

651

AN:

4802

European-Finnish (FIN)

AF:

0.261

AC:

2763

AN:

10580

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.297

AC:

20168

AN:

67958

Other (OTH)

AF:

0.222

AC:

469

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1203

2405

3608

4810

6013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.271

Hom.:

10138

Bravo

AF:

0.204

Asia WGS

AF:

0.167

AC:

584

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.5

(source)

DANN

Benign

0.44

PhyloP100

0.0030

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over