Variant 12-6845460-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001297603.3(CDCA3):c.*1328C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 656,438 control chromosomes in the GnomAD database, including 48,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 17343 hom., cov: 32)

Exomes 𝑓: 0.34 ( 31211 hom. )

Consequence

CDCA3
NM_001297603.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.452

Variant links:

Genes affected

GNB3 (HGNC:4400): (G protein subunit beta 3) Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit which belongs to the WD repeat G protein beta family. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. A single-nucleotide polymorphism (C825T) in this gene is associated with essential hypertension and obesity. This polymorphism is also associated with the occurrence of the splice variant GNB3-s, which appears to have increased activity. GNB3-s is an example of alternative splicing caused by a nucleotide change outside of the splice donor and acceptor sites. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Jul 2014]

GNB3 links:

CDCA3 (HGNC:14624): (cell division cycle associated 3) Predicted to be involved in cell division and protein ubiquitination. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

CDCA3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 12-6845460-G-A is Benign according to our data. Variant chr12-6845460-G-A is described in ClinVar as [Benign]. Clinvar id is 675808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNB3	NM_002075.4 link	c.700-126G>A		intron_variant		ENST00000229264.8	NP_002066.1	P16520-1F1T0G5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNB3	ENST00000229264.8 link	c.700-126G>A		intron_variant		5	NM_002075.4	ENSP00000229264.3		P16520-1

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

66597

AN:

151990

Hom.:

17312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.735

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.507

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.443

GnomAD4 exome

AF:

0.336

AC:

169536

AN:

504332

Hom.:

31211

Cov.:

AF XY:

0.333

AC XY:

88590

AN XY:

266230

show subpopulations

Gnomad4 AFR exome

AF:

0.746

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.318

Gnomad4 EAS exome

AF:

0.509

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.265

Gnomad4 NFE exome

AF:

0.305

Gnomad4 OTH exome

AF:

0.366

GnomAD4 genome

AF:

0.438

AC:

66687

AN:

152106

Hom.:

17343

Cov.:

AF XY:

0.434

AC XY:

32257

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.735

Gnomad4 AMR

AF:

0.401

Gnomad4 ASJ

AF:

0.316

Gnomad4 EAS

AF:

0.507

Gnomad4 SAS

AF:

0.315

Gnomad4 FIN

AF:

0.255

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.447

Alfa

AF:

0.309

Hom.:

4704

Bravo

AF:

0.466

Asia WGS

AF:

0.416

AC:

1446

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.78

DANN

Benign

0.68

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over