1-1834144-T-C

Variant summary

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

The NM_002074.5(GNB1):c.-47+5046A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 151,916 control chromosomes in the GnomAD database, including 54,713 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 0.83 (54713 hom., cov: 30)
• Consequence: GNB1 NM_002074.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354

Genes affected

GNB1 (HGNC:4396): (G protein subunit beta 1) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNB1	NM_002074.5	c.-47+5046A>G		intron_variant		ENST00000378609.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB1	ENST00000378609.9	c.-47+5046A>G		intron_variant		1	NM_002074.5	P1

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126622 AN: 151798 Hom.: 54688 Cov.: 30

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.857

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.834 AC: 126699 AN: 151916 Hom.: 54713 Cov.: 30 AF XY: 0.831 AC XY: 61688 AN XY: 74252

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.896

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.928

Gnomad4 NFE AF: 0.950

Gnomad4 OTH AF: 0.858

Alfa AF: 0.846 Hom.: 4432

Bravo AF: 0.827

Asia WGS AF: 0.796 AC: 2768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.7
Dann	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6603797; hg19: chr1-1765583;