dbSNP rs622491: CCDC3:c.-269-8500T>G (chr10-13058441-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001282658.2(CCDC3):c.-269-8500T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 760,780 control chromosomes in the GnomAD database, including 42,061 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 0.35 ( 9652 hom., cov: 33)

Exomes 𝑓: 0.32 ( 32409 hom. )

Consequence

CCDC3
NM_001282658.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.777

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:

RPL5P25 (HGNC:35493): (ribosomal protein L5 pseudogene 25)

RPL5P25 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC3	NM_001282658.2 link	c.-269-8500T>G		intron_variant	Intron 4 of 6		NP_001269587.1	Q9BQI4-2
RPL5P25		n.13058441A>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC3	ENST00000378839.1 link	c.-269-8500T>G		intron_variant	Intron 4 of 6	2		ENSP00000368116.1		Q9BQI4-2
RPL5P25	ENST00000441148.1 link	n.236T>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53272

AN:

152016

Hom.:

9646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.400

Gnomad AMI

AF:

0.505

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.328

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.332

GnomAD4 exome

AF:

0.316

AC:

192362

AN:

608646

Hom.:

32409

Cov.:

AF XY:

0.309

AC XY:

102716

AN XY:

332106

show subpopulations

Gnomad4 AFR exome

AF:

0.407

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.337

Gnomad4 EAS exome

AF:

0.143

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.284

Gnomad4 NFE exome

AF:

0.351

Gnomad4 OTH exome

AF:

0.326

GnomAD4 genome

AF:

0.350

AC:

53310

AN:

152134

Hom.:

9652

Cov.:

AF XY:

0.346

AC XY:

25721

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.400

Gnomad4 AMR

AF:

0.374

Gnomad4 ASJ

AF:

0.337

Gnomad4 EAS

AF:

0.132

Gnomad4 SAS

AF:

0.190

Gnomad4 FIN

AF:

0.279

Gnomad4 NFE

AF:

0.354

Gnomad4 OTH

AF:

0.329

Alfa

AF:

0.347

Hom.:

1132

Bravo

AF:

0.364

Asia WGS

AF:

0.168

AC:

584

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.4

DANN

Benign

0.37

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over