dbSNP rs3774225: GNB4:c.*3G>A (chr3-179401210-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_021629.4(GNB4):c.*3G>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 0.175 in 1,595,862 control chromosomes in the GnomAD database, including 25,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2264 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23248 hom. )

Consequence

GNB4
NM_021629.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.809

Variant links:

Genes affected

GNB4 (HGNC:20731): (G protein subunit beta 4) 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. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. [provided by RefSeq, Jul 2008]

GNB4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 3-179401210-C-T is Benign according to our data. Variant chr3-179401210-C-T is described in ClinVar as [Benign]. Clinvar id is 261426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-179401210-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB4	NM_021629.4 link	c.*3G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000232564.8	NP_067642.1	Q9HAV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB4	ENST00000232564.8 link	c.*3G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_021629.4	ENSP00000232564.3		Q9HAV0

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25573

AN:

151944

Hom.:

2263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.237

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.184

GnomAD2 exomes

AF:

0.191

AC:

47755

AN:

249404

AF XY:

0.190

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.283

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.155

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.196

GnomAD4 exome

AF:

0.176

AC:

253401

AN:

1443800

Hom.:

23248

Cov.:

AF XY:

0.176

AC XY:

126713

AN XY:

719404

show subpopulations

African (AFR)

AF:

0.128

AC:

4246

AN:

33074

American (AMR)

AF:

0.276

AC:

12248

AN:

44332

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

4471

AN:

25974

East Asian (EAS)

AF:

0.229

AC:

9036

AN:

39510

South Asian (SAS)

AF:

0.198

AC:

16944

AN:

85524

European-Finnish (FIN)

AF:

0.151

AC:

8050

AN:

53354

Middle Eastern (MID)

AF:

0.215

AC:

1227

AN:

5700

European-Non Finnish (NFE)

AF:

0.170

AC:

186342

AN:

1096588

Other (OTH)

AF:

0.181

AC:

10837

AN:

59744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

9130

18260

27389

36519

45649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.168

AC:

25579

AN:

152062

Hom.:

2264

Cov.:

AF XY:

0.171

AC XY:

12734

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.130

AC:

5385

AN:

41508

American (AMR)

AF:

0.226

AC:

3460

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

612

AN:

3466

East Asian (EAS)

AF:

0.237

AC:

1224

AN:

5166

South Asian (SAS)

AF:

0.202

AC:

972

AN:

4820

European-Finnish (FIN)

AF:

0.150

AC:

1578

AN:

10524

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.173

AC:

11748

AN:

67984

Other (OTH)

AF:

0.183

AC:

386

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1066

2132

3198

4264

5330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.179

Hom.:

4254

Bravo

AF:

0.175

Asia WGS

AF:

0.229

AC:

799

AN:

3478

EpiCase

AF:

0.179

EpiControl

AF:

0.178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.29

CADD

Benign

9.5

(source)

DANN

Benign

0.81

PhyloP100

0.81

Mutation Taster

=100/0

polymorphism (auto)

(source)

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 for variant 3:179401210 C>T . It may be empty.

rs3774225

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over