rs10907185

chr1-1801780-A-Gchr1-1801780-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNB1	NM_002074.5	c.430+2639T>C		intron_variant		ENST00000378609.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB1	ENST00000378609.9	c.430+2639T>C		intron_variant		1	NM_002074.5	P1

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

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.617

Alfa AF: 0.654 Hom.: 13012

Bravo AF: 0.559

Asia WGS AF: 0.652 AC: 2266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.34
Dann	Benign	0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs10907185; hg19: chr1-1733219;