rs1553191393

Variant names:

• chr1-1787340-GATC-G
• rs1553191393
• NM_002074.5:c.1011_1013delGAT

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4_Supporting PP5_Moderate

The NM_002074.5(GNB1):​c.1011_1013delGAT​(p.Lys337_Ile338delinsAsn) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNB1 NM_002074.5 disruptive_inframe_deletion
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.12
• Publications: 0 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

ENSG00000302550 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_002074.5. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 1-1787340-GATC-G is Pathogenic according to our data. Variant chr1-1787340-GATC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 521025.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1011_1013delGAT	p.Lys337_Ile338delinsAsn	disruptive_inframe_deletion	Exon 11 of 12	NP_002065.1	P62873-1
	GNB1	NM_001282539.2		c.1011_1013delGAT	p.Lys337_Ile338delinsAsn	disruptive_inframe_deletion	Exon 10 of 11	NP_001269468.1	A0A140VJJ8
	GNB1	NM_001282538.2		c.711_713delGAT	p.Lys237_Ile238delinsAsn	disruptive_inframe_deletion	Exon 9 of 10	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.1011_1013delGAT	p.Lys337_Ile338delinsAsn	disruptive_inframe_deletion	Exon 11 of 12	ENSP00000367872.3	P62873-1
	GNB1	ENST00000947520.1		c.1065_1067delGAT	p.Lys355_Ile356delinsAsn	disruptive_inframe_deletion	Exon 12 of 13	ENSP00000617579.1
	GNB1	ENST00000947524.1		c.1047_1049delGAT	p.Lys349_Ile350delinsAsn	disruptive_inframe_deletion	Exon 12 of 13	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

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.1
Mutation Taster		=18/182	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1553191393; hg19: chr1-1718779;