12-6845460-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001297603.3(CDCA3):​c.*1328C>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 0.000202 in 657,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: CDCA3 NM_001297603.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-6845460-G-T is Benign according to our data. Variant chr12-6845460-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1047849.Status of the report is criteria_provided_single_submitter, 1 stars.

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>T		intron	N/A	NP_002066.1	P16520-1
	CDCA3	NM_001297603.3		c.*1328C>A		3_prime_UTR	Exon 5 of 5	NP_001284532.1	F8WDL1
	GNB3	NM_001297571.2		c.697-126G>T		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>T		intron	N/A	ENSP00000229264.3	P16520-1
	GNB3	ENST00000435982.6	TSL:1	c.697-126G>T		intron	N/A	ENSP00000414734.2	E9PCP0
	CDCA3	ENST00000422785.7	TSL:2	c.*1328C>A		3_prime_UTR	Exon 5 of 5	ENSP00000415142.2	F8WDL1

Frequencies

GnomAD3 genomes AF: 0.000638 AC: 97 AN: 152046 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.0000673 AC: 34 AN: 504890 Hom.: 0 Cov.: 6 AF XY: 0.0000750 AC XY: 20 AN XY: 266516

African (AFR) AF: 0.00183 AC: 26 AN: 14226

American (AMR) AF: 0.0000750 AC: 2 AN: 26650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15306

East Asian (EAS) AF: 0.00 AC: 0 AN: 31570

South Asian (SAS) AF: 0.00 AC: 0 AN: 52258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2204

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 303590

Other (OTH) AF: 0.000213 AC: 6 AN: 28124

GnomAD4 genome AF: 0.000651 AC: 99 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.000565 AC XY: 42 AN XY: 74380

African (AFR) AF: 0.00224 AC: 93 AN: 41506

American (AMR) AF: 0.000262 AC: 4 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00 Hom.: 24492

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.2
DANN	Benign	0.74
PhyloP100		-0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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;