rs7618348

chr3-179426951-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNB4	NM_021629.4	c.-42-709G>A		intron_variant		ENST00000232564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB4	ENST00000232564.8	c.-42-709G>A		intron_variant		1	NM_021629.4	P1

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

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.398

Alfa AF: 0.415 Hom.: 6286

Bravo AF: 0.400

Asia WGS AF: 0.379 AC: 1318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.2
Dann	Benign	0.44

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

LitVar

Other links and lift over

dbSNP: rs7618348; hg19: chr3-179144739;