NM_002075.4:c.*118C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002075.4(GNB3):​c.*118C>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 0.057 in 658,528 control chromosomes in the GnomAD database, including 4,634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 2012 hom., cov: 33)
Exomes 𝑓: 0.044 ( 2622 hom. )

Consequence

GNB3
NM_002075.4 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.286

Publications

11 publications found
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]
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
Variant 12-6847016-C-T is Benign according to our data. Variant chr12-6847016-C-T is described in CliVar as Benign. Clinvar id is 1260978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-6847016-C-T is described in CliVar as Benign. Clinvar id is 1260978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GNB3NM_002075.4 linkc.*118C>T 3_prime_UTR_variant Exon 10 of 10 ENST00000229264.8 NP_002066.1 P16520-1F1T0G5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GNB3ENST00000229264.8 linkc.*118C>T 3_prime_UTR_variant Exon 10 of 10 5 NM_002075.4 ENSP00000229264.3 P16520-1

Frequencies

GnomAD3 genomes
AF:
0.100
AC:
15280
AN:
152140
Hom.:
1994
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.275
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.107
Gnomad ASJ
AF:
0.00634
Gnomad EAS
AF:
0.301
Gnomad SAS
AF:
0.0151
Gnomad FIN
AF:
0.00160
Gnomad MID
AF:
0.0728
Gnomad NFE
AF:
0.00556
Gnomad OTH
AF:
0.0989
GnomAD4 exome
AF:
0.0438
AC:
22171
AN:
506270
Hom.:
2622
Cov.:
6
AF XY:
0.0391
AC XY:
10430
AN XY:
266548
show subpopulations
African (AFR)
AF:
0.281
AC:
4145
AN:
14774
American (AMR)
AF:
0.125
AC:
3783
AN:
30204
Ashkenazi Jewish (ASJ)
AF:
0.00823
AC:
133
AN:
16156
East Asian (EAS)
AF:
0.325
AC:
10162
AN:
31286
South Asian (SAS)
AF:
0.0115
AC:
606
AN:
52762
European-Finnish (FIN)
AF:
0.00198
AC:
68
AN:
34332
Middle Eastern (MID)
AF:
0.0557
AC:
123
AN:
2210
European-Non Finnish (NFE)
AF:
0.00552
AC:
1636
AN:
296398
Other (OTH)
AF:
0.0538
AC:
1515
AN:
28148
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
837
1675
2512
3350
4187
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
202
404
606
808
1010
<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:
0.101
AC:
15346
AN:
152258
Hom.:
2012
Cov.:
33
AF XY:
0.101
AC XY:
7514
AN XY:
74462
show subpopulations
African (AFR)
AF:
0.275
AC:
11431
AN:
41522
American (AMR)
AF:
0.107
AC:
1637
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.00634
AC:
22
AN:
3472
East Asian (EAS)
AF:
0.301
AC:
1558
AN:
5172
South Asian (SAS)
AF:
0.0149
AC:
72
AN:
4828
European-Finnish (FIN)
AF:
0.00160
AC:
17
AN:
10628
Middle Eastern (MID)
AF:
0.0680
AC:
20
AN:
294
European-Non Finnish (NFE)
AF:
0.00556
AC:
378
AN:
68028
Other (OTH)
AF:
0.0997
AC:
211
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
578
1156
1734
2312
2890
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
154
308
462
616
770
<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:
0.0421
Hom.:
2492
Bravo
AF:
0.119
Asia WGS
AF:
0.127
AC:
443
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

May 12, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
CADD
Benign
9.0
DANN
Benign
0.80
PhyloP100
-0.29
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
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

Publications

Other links and lift over

dbSNP: rs5445; hg19: chr12-6956180; COSMIC: COSV57529079; COSMIC: COSV57529079; API