rs7618348

Variant names:

• chr3-179426951-C-T
• rs7618348
• NM_021629.4:c.-42-709G>A

Variant summary

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

The NM_021629.4(GNB4):​c.-42-709G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,738 control chromosomes in the GnomAD database, including 12,567 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 0.40 (12567 hom., cov: 30)
• Consequence: GNB4 NM_021629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021629.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB4	NM_021629.4	MANE Select	c.-42-709G>A		intron	N/A	NP_067642.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB4	ENST00000232564.8	TSL:1 MANE Select	c.-42-709G>A		intron	N/A	ENSP00000232564.3
	GNB4	ENST00000674862.1		c.-25-726G>A		intron	N/A	ENSP00000502628.1
	GNB4	ENST00000676128.1		c.-42-709G>A		intron	N/A	ENSP00000501882.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61135 AN: 151620 Hom.: 12558 Cov.: 30

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.403 AC: 61166 AN: 151738 Hom.: 12567 Cov.: 30 AF XY: 0.411 AC XY: 30485 AN XY: 74128

African (AFR) AF: 0.349 AC: 14430 AN: 41364

American (AMR) AF: 0.501 AC: 7642 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1360 AN: 3466

East Asian (EAS) AF: 0.298 AC: 1524 AN: 5114

South Asian (SAS) AF: 0.410 AC: 1967 AN: 4802

European-Finnish (FIN) AF: 0.478 AC: 5027 AN: 10506

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27940 AN: 67920

Other (OTH) AF: 0.398 AC: 839 AN: 2108

Alfa AF: 0.414 Hom.: 6969

Bravo AF: 0.400

Asia WGS AF: 0.379 AC: 1318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.44
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7618348; hg19: chr3-179144739;