3-179419485-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021629.4(GNB4):c.117T>C(p.Ser39Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,601,116 control chromosomes in the GnomAD database, including 177,775 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 16872 hom., cov: 32)

Exomes 𝑓: 0.47 ( 160903 hom. )

Consequence

GNB4
NM_021629.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.67

Publications

29 publications found

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 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease dominant intermediate F
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
Charcot-Marie-Tooth disease
Inheritance: AD Classification: MODERATE Submitted by: ClinGen

GNB4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-179419485-A-G is Benign according to our data. Variant chr3-179419485-A-G is described in ClinVar as Benign. ClinVar VariationId is 261427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB4	NM_021629.4 link	c.117T>C	p.Ser39Ser	synonymous_variant	Exon 4 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.117T>C	p.Ser39Ser	synonymous_variant	Exon 4 of 10	1	NM_021629.4	ENSP00000232564.3		Q9HAV0

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71358

AN:

151818

Hom.:

16851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.452

Gnomad AMI

AF:

0.463

Gnomad AMR

AF:

0.516

Gnomad ASJ

AF:

0.476

Gnomad EAS

AF:

0.436

Gnomad SAS

AF:

0.511

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.464

Gnomad OTH

AF:

0.471

GnomAD2 exomes

AF:

0.476

AC:

119489

AN:

251164

AF XY:

0.478

show subpopulations

Gnomad AFR exome

AF:

0.448

Gnomad AMR exome

AF:

0.503

Gnomad ASJ exome

AF:

0.475

Gnomad EAS exome

AF:

0.429

Gnomad FIN exome

AF:

0.500

Gnomad NFE exome

AF:

0.464

Gnomad OTH exome

AF:

0.473

GnomAD4 exome

AF:

0.469

AC:

679732

AN:

1449180

Hom.:

160903

Cov.:

AF XY:

0.472

AC XY:

340343

AN XY:

721738

show subpopulations

African (AFR)

AF:

0.445

AC:

14761

AN:

33206

American (AMR)

AF:

0.504

AC:

22500

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

12543

AN:

26032

East Asian (EAS)

AF:

0.464

AC:

18374

AN:

39608

South Asian (SAS)

AF:

0.515

AC:

44233

AN:

85938

European-Finnish (FIN)

AF:

0.505

AC:

26981

AN:

53390

Middle Eastern (MID)

AF:

0.422

AC:

2428

AN:

5750

European-Non Finnish (NFE)

AF:

0.463

AC:

509789

AN:

1100660

Other (OTH)

AF:

0.469

AC:

28123

AN:

59948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

15986

31972

47957

63943

79929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15162

30324

45486

60648

75810

<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:

0.470

AC:

71404

AN:

151936

Hom.:

16872

Cov.:

AF XY:

0.471

AC XY:

34976

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.451

AC:

18703

AN:

41426

American (AMR)

AF:

0.516

AC:

7882

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

1651

AN:

3468

East Asian (EAS)

AF:

0.436

AC:

2250

AN:

5164

South Asian (SAS)

AF:

0.509

AC:

2454

AN:

4820

European-Finnish (FIN)

AF:

0.512

AC:

5391

AN:

10530

Middle Eastern (MID)

AF:

0.373

AC:

109

AN:

292

European-Non Finnish (NFE)

AF:

0.464

AC:

31539

AN:

67944

Other (OTH)

AF:

0.476

AC:

1004

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1948

3896

5845

7793

9741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

644

1288

1932

2576

3220

<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:

0.466

Hom.:

26414

Bravo

AF:

0.466

Asia WGS

AF:

0.491

AC:

1703

AN:

3478

EpiCase

AF:

0.469

EpiControl

AF:

0.476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 05, 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

- -

Charcot-Marie-Tooth disease dominant intermediate F

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.87

CADD

Benign

2.4

(source)

DANN

Benign

0.55

PhyloP100

-2.7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over