rs7612445

Variant names:

• chr3-179455191-G-T
• rs7612445
• XM_047448653.1:c.-42-28949C>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.-42-28949C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,072 control chromosomes in the GnomAD database, including 5,013 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 0.24 (5013 hom., cov: 32)
• Consequence: GNB4 XM_047448653.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509
• Publications: 39 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: Orphanet, Labcorp Genetics (formerly Invitae)
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36764 AN: 151954 Hom.: 4990 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.242 AC: 36831 AN: 152072 Hom.: 5013 Cov.: 32 AF XY: 0.242 AC XY: 18004 AN XY: 74350

African (AFR) AF: 0.357 AC: 14816 AN: 41456

American (AMR) AF: 0.254 AC: 3873 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1029 AN: 3468

East Asian (EAS) AF: 0.169 AC: 878 AN: 5184

South Asian (SAS) AF: 0.249 AC: 1199 AN: 4810

European-Finnish (FIN) AF: 0.111 AC: 1171 AN: 10592

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12813 AN: 67974

Other (OTH) AF: 0.276 AC: 581 AN: 2108

Alfa AF: 0.211 Hom.: 15093

Bravo AF: 0.260

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.49
DANN	Benign	0.54
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs7612445; hg19: chr3-179172979;