chr3-179406069-A-G

Variant names:

• chr3-179406069-A-G
• rs17293193
• NM_021629.4:c.700-663T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021629.4(GNB4):​c.700-663T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,178 control chromosomes in the GnomAD database, including 1,371 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 0.12 (1371 hom., cov: 32)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: GNB4 NM_021629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

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]

ENSG00000272699 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB4	NM_021629.4	c.700-663T>C		intron_variant	Intron 8 of 9	ENST00000232564.8	NP_067642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB4	ENST00000232564.8	c.700-663T>C		intron_variant	Intron 8 of 9	1	NM_021629.4	ENSP00000232564.3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17679 AN: 152050 Hom.: 1371 Cov.: 32

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0397

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.200 AC: 2 AN: 10 Hom.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.116 AC: 17674 AN: 152168 Hom.: 1371 Cov.: 32 AF XY: 0.115 AC XY: 8523 AN XY: 74398

Gnomad4 AFR AF: 0.0323

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0400

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.140

Alfa AF: 0.152 Hom.: 237

Bravo AF: 0.114

Asia WGS AF: 0.0290 AC: 103 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.93
DANN	Benign	0.41

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: rs17293193; hg19: chr3-179123857;