dbSNP rs17293193: GNB4:c.700-663T>C (chr3-179406069-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021629.4(GNB4):c.700-663T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,178 control chromosomes in the GnomAD database, including 1,371 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1371 hom., cov: 32)

Exomes 𝑓: 0.20 ( 0 hom. )

Consequence

GNB4
NM_021629.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.232

Publications

2 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:

ENSG00000272699 (HGNC:):

ENSG00000272699 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB4	NM_021629.4 link	c.700-663T>C		intron_variant	Intron 8 of 9	ENST00000232564.8	NP_067642.1	Q9HAV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB4	ENST00000232564.8 link	c.700-663T>C		intron_variant	Intron 8 of 9	1	NM_021629.4	ENSP00000232564.3		Q9HAV0

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17679

AN:

152050

Hom.:

1371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0324

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0397

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.142

GnomAD4 exome

AF:

0.200

AC:

AN:

Hom.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.116

AC:

17674

AN:

152168

Hom.:

1371

Cov.:

AF XY:

0.115

AC XY:

8523

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0323

AC:

1341

AN:

41522

American (AMR)

AF:

0.124

AC:

1887

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

518

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5178

South Asian (SAS)

AF:

0.0400

AC:

193

AN:

4828

European-Finnish (FIN)

AF:

0.136

AC:

1442

AN:

10588

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.174

AC:

11823

AN:

67992

Other (OTH)

AF:

0.140

AC:

296

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

752

1504

2257

3009

3761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

194

388

582

776

970

<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:

0.141

Hom.:

491

Bravo

AF:

0.114

Asia WGS

AF:

0.0290

AC:

103

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.93

(source)

DANN

Benign

0.41

PhyloP100

-0.23

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over