3-179460067-C-T

Variant names:

• chr3-179460067-C-T
• rs754574
• XM_047448653.1:c.-42-33825G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047448653.1(GNB4):​c.-42-33825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,136 control chromosomes in the GnomAD database, including 8,575 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 0.32 (8575 hom., cov: 33)
• Consequence: GNB4 XM_047448653.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524
• Publications: 7 publications found

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: Labcorp Genetics (formerly Invitae), Orphanet
• Charcot-Marie-Tooth disease

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49333 AN: 152020 Hom.: 8567 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.313

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.325 AC: 49370 AN: 152136 Hom.: 8575 Cov.: 33 AF XY: 0.322 AC XY: 23991 AN XY: 74394

African (AFR) AF: 0.457 AC: 18977 AN: 41490

American (AMR) AF: 0.246 AC: 3767 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3468

East Asian (EAS) AF: 0.246 AC: 1275 AN: 5186

South Asian (SAS) AF: 0.282 AC: 1362 AN: 4822

European-Finnish (FIN) AF: 0.250 AC: 2644 AN: 10574

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19295 AN: 67990

Other (OTH) AF: 0.309 AC: 653 AN: 2110

Alfa AF: 0.308 Hom.: 3312

Bravo AF: 0.328

Asia WGS AF: 0.266 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.40
PhyloP100		0.52

Splicing

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

Other links and lift over

dbSNP: rs754574; hg19: chr3-179177855;