3-179401210-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_021629.4(GNB4):c.*3G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,595,862 control chromosomes in the GnomAD database, including 25,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2264 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23248 hom.)
• Consequence: GNB4 NM_021629.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.809

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 3-179401210-C-T is Benign according to our data. Variant chr3-179401210-C-T is described in ClinVar as [Benign]. Clinvar id is 261426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-179401210-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNB4	NM_021629.4	c.*3G>A		3_prime_UTR_variant	10/10	ENST00000232564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB4	ENST00000232564.8	c.*3G>A		3_prime_UTR_variant	10/10	1	NM_021629.4	P1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25573 AN: 151944 Hom.: 2263 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.184

GnomAD3 exomes AF: 0.191 AC: 47755 AN: 249404 Hom.: 4967 AF XY: 0.190 AC XY: 25577 AN XY: 134964

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.221

Gnomad SAS exome AF: 0.199

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.196

GnomAD4 exome AF: 0.176 AC: 253401 AN: 1443800 Hom.: 23248 Cov.: 26 AF XY: 0.176 AC XY: 126713 AN XY: 719404

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.276

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.168 AC: 25579 AN: 152062 Hom.: 2264 Cov.: 32 AF XY: 0.171 AC XY: 12734 AN XY: 74310

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.183

Alfa AF: 0.177 Hom.: 3125

Bravo AF: 0.175

Asia WGS AF: 0.229 AC: 799 AN: 3478

EpiCase AF: 0.179

EpiControl AF: 0.178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	9.5
Dann	Benign	0.81

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: rs3774225; hg19: chr3-179118998; COSMIC: COSV51708721; COSMIC: COSV51708721;