rs4648727

Variant names:

• chr1-1844830-C-A
• rs4648727
• NM_002074.5:c.-95-5592G>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.-95-5592G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,004 control chromosomes in the GnomAD database, including 12,911 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 0.41 (12911 hom., cov: 32)
• Consequence: GNB1 NM_002074.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878
• Publications: 18 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB1	NM_002074.5	c.-95-5592G>T		intron_variant	Intron 1 of 11	ENST00000378609.9	NP_002065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB1	ENST00000378609.9	c.-95-5592G>T		intron_variant	Intron 1 of 11	1	NM_002074.5	ENSP00000367872.3

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62149 AN: 151886 Hom.: 12913 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.409 AC: 62161 AN: 152004 Hom.: 12911 Cov.: 32 AF XY: 0.407 AC XY: 30251 AN XY: 74292

African (AFR) AF: 0.395 AC: 16358 AN: 41464

American (AMR) AF: 0.339 AC: 5178 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1727 AN: 3468

East Asian (EAS) AF: 0.336 AC: 1738 AN: 5168

South Asian (SAS) AF: 0.355 AC: 1714 AN: 4822

European-Finnish (FIN) AF: 0.414 AC: 4366 AN: 10556

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29739 AN: 67950

Other (OTH) AF: 0.406 AC: 858 AN: 2114

Alfa AF: 0.433 Hom.: 56116

Bravo AF: 0.406

Asia WGS AF: 0.296 AC: 1036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		-0.88
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: rs4648727; hg19: chr1-1776269;