1-1834144-T-C

Variant names:

• chr1-1834144-T-C
• rs6603797
• NM_002074.5:c.-47+5046A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

GNB1 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 42

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GNB1	NM_002074.5	c.-47+5046A>G		intron_variant	Intron 2 of 11	ENST00000378609.9	NP_002065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB1	ENST00000378609.9	c.-47+5046A>G		intron_variant	Intron 2 of 11	1	NM_002074.5	ENSP00000367872.3

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

African (AFR) AF: 0.594 AC: 24577 AN: 41358

American (AMR) AF: 0.896 AC: 13667 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3152 AN: 3470

East Asian (EAS) AF: 0.887 AC: 4559 AN: 5140

South Asian (SAS) AF: 0.702 AC: 3369 AN: 4796

European-Finnish (FIN) AF: 0.928 AC: 9823 AN: 10582

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.950 AC: 64618 AN: 68002

Other (OTH) AF: 0.858 AC: 1814 AN: 2114

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
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6603797; hg19: chr1-1765583;