rs79370402

Variant names:

• chr1-1787203-C-A
• rs79370402
• NM_002074.5:c.*9+119G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen

ENSG00000302550 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002074.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB1	NM_002074.5	MANE Select	c.*9+119G>T		intron	N/A	NP_002065.1	P62873-1
	GNB1	NM_001282539.2		c.*9+119G>T		intron	N/A	NP_001269468.1	A0A140VJJ8
	GNB1	NM_001282538.2		c.*9+119G>T		intron	N/A	NP_001269467.1	B3KVK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB1	ENST00000378609.9	TSL:1 MANE Select	c.*9+119G>T		intron	N/A	ENSP00000367872.3	P62873-1
	GNB1	ENST00000703692.1		c.*128G>T		3_prime_UTR	Exon 11 of 11	ENSP00000515427.1	P62873-1
	GNB1	ENST00000703694.1		c.*128G>T		3_prime_UTR	Exon 10 of 10	ENSP00000515429.1	P62873-1

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

African (AFR) AF: 0.0160 AC: 221 AN: 13798

American (AMR) AF: 0.0405 AC: 961 AN: 23752

Ashkenazi Jewish (ASJ) AF: 0.0491 AC: 700 AN: 14266

East Asian (EAS) AF: 0.000125 AC: 4 AN: 31986

South Asian (SAS) AF: 0.0201 AC: 991 AN: 49380

European-Finnish (FIN) AF: 0.0360 AC: 1572 AN: 43652

Middle Eastern (MID) AF: 0.0444 AC: 162 AN: 3646

European-Non Finnish (NFE) AF: 0.0806 AC: 25003 AN: 310074

Other (OTH) AF: 0.0596 AC: 1663 AN: 27916

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

African (AFR) AF: 0.0157 AC: 654 AN: 41544

American (AMR) AF: 0.0553 AC: 846 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.0155 AC: 75 AN: 4828

European-Finnish (FIN) AF: 0.0302 AC: 320 AN: 10608

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0836 AC: 5686 AN: 68030

Other (OTH) AF: 0.0685 AC: 145 AN: 2116

Alfa AF: 0.0655 Hom.: 37

Bravo AF: 0.0537

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.55
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs79370402; hg19: chr1-1718642;