rs9306226

Variant names:

• chr22-19829910-T-C
• rs9306226
• NM_053004.3:c.-20-8535A>G

Variant summary

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

The NM_053004.3(GNB1L):​c.-20-8535A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,082 control chromosomes in the GnomAD database, including 5,111 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 0.26 (5111 hom., cov: 32)
• Consequence: GNB1L NM_053004.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378
• Publications: 0 publications found

Genes affected

GNB1L (HGNC:4397): (G protein subunit beta 1 like) This gene encodes a G-protein beta-subunit-like polypeptide which is a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 6 WD repeats and is highly expressed in the heart. The gene maps to the region on chromosome 22q11, which is deleted in DiGeorge syndrome, trisomic in derivative 22 syndrome and tetrasomic in cat-eye syndrome. Therefore, this gene may contribute to the etiology of those disorders. Transcripts from this gene share exons with some transcripts from the C22orf29 gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB1L	NM_053004.3	c.-20-8535A>G		intron_variant	Intron 2 of 7	ENST00000329517.11	NP_443730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB1L	ENST00000329517.11	c.-20-8535A>G		intron_variant	Intron 2 of 7	1	NM_053004.3	ENSP00000331313.6

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38975 AN: 151968 Hom.: 5105 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.256 AC: 39004 AN: 152082 Hom.: 5111 Cov.: 32 AF XY: 0.251 AC XY: 18652 AN XY: 74342

African (AFR) AF: 0.222 AC: 9208 AN: 41462

American (AMR) AF: 0.248 AC: 3791 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1690 AN: 5182

South Asian (SAS) AF: 0.167 AC: 802 AN: 4814

European-Finnish (FIN) AF: 0.218 AC: 2307 AN: 10566

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.284 AC: 19322 AN: 67980

Other (OTH) AF: 0.260 AC: 550 AN: 2116

Alfa AF: 0.271 Hom.: 1948

Bravo AF: 0.262

Asia WGS AF: 0.244 AC: 846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.37
PhyloP100		0.38
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: rs9306226; hg19: chr22-19817433;