3-179401322-GA-G

Position:

• chr3-179401322-GA-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_021629.4(GNB4):​c.917-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000046 in 1,586,640 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: GNB4 NM_021629.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.106

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 3-179401322-GA-G is Benign according to our data. Variant chr3-179401322-GA-G is described in ClinVar as [Benign]. Clinvar id is 540921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 72 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNB4	NM_021629.4	c.917-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000232564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB4	ENST00000232564.8	c.917-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_021629.4	P1

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150828 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000501 AC: 72 AN: 1435812 Hom.: 0 Cov.: 28 AF XY: 0.0000476 AC XY: 34 AN XY: 714184

Gnomad4 AFR exome AF: 0.0000620

Gnomad4 AMR exome AF: 0.000265

Gnomad4 ASJ exome AF: 0.0000393

Gnomad4 EAS exome AF: 0.000179

Gnomad4 SAS exome AF: 0.0000724

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.0000374

Gnomad4 OTH exome AF: 0.0000507

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150828 Hom.: 0 Cov.: 33 AF XY: 0.0000136 AC XY: 1 AN XY: 73568

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth disease dominant intermediate F Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 13, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs764075662; hg19: chr3-179119110;