rs10907185

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-1801780-A-G
• chr1-1801780-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002074.5(GNB1):​c.430+2639T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,094 control chromosomes in the GnomAD database, including 27,607 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 0.57 (27607 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 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.430+2639T>C		intron	N/A	NP_002065.1	P62873-1
	GNB1	NM_001282539.2		c.430+2639T>C		intron	N/A	NP_001269468.1	A0A140VJJ8
	GNB1	NM_001282538.2		c.130+2639T>C		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>C		intron	N/A	ENSP00000367872.3	P62873-1
	GNB1	ENST00000947520.1		c.430+2639T>C		intron	N/A	ENSP00000617579.1
	GNB1	ENST00000947524.1		c.430+2639T>C		intron	N/A	ENSP00000617583.1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86479 AN: 151976 Hom.: 27599 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.569 AC: 86501 AN: 152094 Hom.: 27607 Cov.: 32 AF XY: 0.569 AC XY: 42325 AN XY: 74350

African (AFR) AF: 0.250 AC: 10390 AN: 41494

American (AMR) AF: 0.696 AC: 10619 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2384 AN: 3470

East Asian (EAS) AF: 0.690 AC: 3569 AN: 5176

South Asian (SAS) AF: 0.601 AC: 2902 AN: 4826

European-Finnish (FIN) AF: 0.665 AC: 7038 AN: 10578

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47465 AN: 67972

Other (OTH) AF: 0.617 AC: 1299 AN: 2106

Alfa AF: 0.642 Hom.: 58488

Bravo AF: 0.559

Asia WGS AF: 0.652 AC: 2266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.34
DANN	Benign	0.22
PhyloP100		-1.4
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: rs10907185; hg19: chr1-1733219;