1-1787203-C-A

Position:

• chr1-1787203-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002074.5(GNB1):​c.*9+119G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 670,758 control chromosomes in the GnomAD database, including 1,577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (301 hom., cov: 32)
  • Exomes 𝑓: 0.060 (1276 hom.)
• Consequence: GNB1 NM_002074.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.242

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-1787203-C-A is Benign according to our data. Variant chr1-1787203-C-A is described in ClinVar as [Benign]. Clinvar id is 1279222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNB1	NM_002074.5	c.*9+119G>T		intron_variant		ENST00000378609.9	NP_002065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNB1	ENST00000378609.9	c.*9+119G>T		intron_variant		1	NM_002074.5	ENSP00000367872.3

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 8011 AN: 152170 Hom.: 302 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0836

Gnomad OTH AF: 0.0692

GnomAD4 exome AF: 0.0603 AC: 31277 AN: 518470 Hom.: 1276 Cov.: 6 AF XY: 0.0588 AC XY: 16137 AN XY: 274552

Gnomad4 AFR exome AF: 0.0160

Gnomad4 AMR exome AF: 0.0405

Gnomad4 ASJ exome AF: 0.0491

Gnomad4 EAS exome AF: 0.000125

Gnomad4 SAS exome AF: 0.0201

Gnomad4 FIN exome AF: 0.0360

Gnomad4 NFE exome AF: 0.0806

Gnomad4 OTH exome AF: 0.0596

GnomAD4 genome AF: 0.0526 AC: 8010 AN: 152288 Hom.: 301 Cov.: 32 AF XY: 0.0483 AC XY: 3597 AN XY: 74464

Gnomad4 AFR AF: 0.0157

Gnomad4 AMR AF: 0.0553

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0155

Gnomad4 FIN AF: 0.0302

Gnomad4 NFE AF: 0.0836

Gnomad4 OTH AF: 0.0685

Alfa AF: 0.0655 Hom.: 37

Bravo AF: 0.0537

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs79370402; hg19: chr1-1718642;