GeneBe

rs764075662

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021629.4(GNB4):​c.917-8_917-4delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,354 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

GNB4
NM_021629.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.22

Publications

0 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

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GNB4NM_021629.4 linkc.917-8_917-4delTTTTT splice_region_variant, intron_variant Intron 9 of 9 ENST00000232564.8 NP_067642.1 Q9HAV0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GNB4ENST00000232564.8 linkc.917-8_917-4delTTTTT splice_region_variant, intron_variant Intron 9 of 9 1 NM_021629.4 ENSP00000232564.3 Q9HAV0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.96e-7
AC:
1
AN:
1436354
Hom.:
0
AF XY:
0.00000140
AC XY:
1
AN XY:
714480
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32300
American (AMR)
AF:
0.00
AC:
0
AN:
41570
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25434
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39118
South Asian (SAS)
AF:
0.00
AC:
0
AN:
82938
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52888
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5662
European-Non Finnish (NFE)
AF:
9.11e-7
AC:
1
AN:
1097254
Other (OTH)
AF:
0.00
AC:
0
AN:
59190
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs764075662; hg19: chr3-179119110; API