1-1801780-A-T

Variant names:

• chr1-1801780-A-T
• rs10907185
• NM_002074.5:c.430+2639T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002074.5(GNB1):​c.430+2639T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: GNB1 NM_002074.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Illumina, ClinGen, G2P, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

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.430+2639T>A		intron	N/A	NP_002065.1	P62873-1
	GNB1	NM_001282539.2		c.430+2639T>A		intron	N/A	NP_001269468.1	A0A140VJJ8
	GNB1	NM_001282538.2		c.130+2639T>A		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.430+2639T>A		intron	N/A	ENSP00000367872.3	P62873-1
	GNB1	ENST00000947520.1		c.430+2639T>A		intron	N/A	ENSP00000617579.1
	GNB1	ENST00000947524.1		c.430+2639T>A		intron	N/A	ENSP00000617583.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.25
DANN	Benign	0.35
PhyloP100		-1.4

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: rs10907185; hg19: chr1-1733219;