3-179401445-AAAT-A

Position:

• chr3-179401445-AAAT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_021629.4(GNB4):​c.917-129_917-127delATT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 437,044 control chromosomes in the GnomAD database, including 11,226 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3029 hom., cov: 27)
  • Exomes 𝑓: 0.23 (8197 hom.)
• Consequence: GNB4 NM_021629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.56

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 -10 ACMG points.

• BP6: Variant 3-179401445-AAAT-A is Benign according to our data. Variant chr3-179401445-AAAT-A is described in ClinVar as [Benign]. Clinvar id is 1253124.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNB4	NM_021629.4	c.917-129_917-127delATT		intron_variant		ENST00000232564.8	NP_067642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNB4	ENST00000232564.8	c.917-129_917-127delATT		intron_variant		1	NM_021629.4	ENSP00000232564.3

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27669 AN: 151396 Hom.: 3017 Cov.: 27

Gnomad AFR AF: 0.0588

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.228 AC: 64977 AN: 285530 Hom.: 8197 AF XY: 0.229 AC XY: 33412 AN XY: 145814

Gnomad4 AFR exome AF: 0.0595

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.283

Gnomad4 EAS exome AF: 0.402

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.183 AC: 27683 AN: 151514 Hom.: 3029 Cov.: 27 AF XY: 0.180 AC XY: 13331 AN XY: 74068

Gnomad4 AFR AF: 0.0586

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.236

Bravo AF: 0.186

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs3832243; hg19: chr3-179119233;