rs2301339

Variant names:

• chr12-6845460-G-A
• rs2301339
• NM_002075.4:c.700-126G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-6845460-G-A
• chr12-6845460-G-T
• chr12-6845460-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.452
• Publications: 33 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297603.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB3	NM_002075.4	MANE Select	c.700-126G>A		intron	N/A	NP_002066.1	P16520-1
	CDCA3	NM_001297603.3		c.*1328C>T		3_prime_UTR	Exon 5 of 5	NP_001284532.1	F8WDL1
	GNB3	NM_001297571.2		c.697-126G>A		intron	N/A	NP_001284500.1	E9PCP0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB3	ENST00000229264.8	TSL:5 MANE Select	c.700-126G>A		intron	N/A	ENSP00000229264.3	P16520-1
	GNB3	ENST00000435982.6	TSL:1	c.697-126G>A		intron	N/A	ENSP00000414734.2	E9PCP0
	CDCA3	ENST00000422785.7	TSL:2	c.*1328C>T		3_prime_UTR	Exon 5 of 5	ENSP00000415142.2	F8WDL1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66597 AN: 151990 Hom.: 17312 Cov.: 32

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.: 6 AF XY: 0.333 AC XY: 88590 AN XY: 266230

African (AFR) AF: 0.746 AC: 10595 AN: 14206

American (AMR) AF: 0.349 AC: 9284 AN: 26572

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 4866 AN: 15300

East Asian (EAS) AF: 0.509 AC: 16074 AN: 31560

South Asian (SAS) AF: 0.318 AC: 16601 AN: 52192

European-Finnish (FIN) AF: 0.265 AC: 8195 AN: 30948

Middle Eastern (MID) AF: 0.446 AC: 981 AN: 2198

European-Non Finnish (NFE) AF: 0.305 AC: 92643 AN: 303252

Other (OTH) AF: 0.366 AC: 10297 AN: 28104

GnomAD4 genome AF: 0.438 AC: 66687 AN: 152106 Hom.: 17343 Cov.: 32 AF XY: 0.434 AC XY: 32257 AN XY: 74340

African (AFR) AF: 0.735 AC: 30478 AN: 41494

American (AMR) AF: 0.401 AC: 6136 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1094 AN: 3466

East Asian (EAS) AF: 0.507 AC: 2617 AN: 5160

South Asian (SAS) AF: 0.315 AC: 1521 AN: 4824

European-Finnish (FIN) AF: 0.255 AC: 2702 AN: 10580

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20732 AN: 67980

Other (OTH) AF: 0.447 AC: 944 AN: 2114

Alfa AF: 0.356 Hom.: 24492

Bravo AF: 0.466

Asia WGS AF: 0.416 AC: 1446 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.78
DANN	Benign	0.68
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2301339; hg19: chr12-6954624; COSMIC: COSV106052571; COSMIC: COSV106052571;