NM_053004.3:c.255-352A>G

Variant names:

• chr22-19812799-T-C
• rs2073765
• NM_053004.3:c.255-352A>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.255-352A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,046 control chromosomes in the GnomAD database, including 6,576 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 0.28 (6576 hom., cov: 33)
• Consequence: GNB1L NM_053004.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB1L	NM_053004.3	c.255-352A>G		intron_variant	Intron 4 of 7	ENST00000329517.11	NP_443730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB1L	ENST00000329517.11	c.255-352A>G		intron_variant	Intron 4 of 7	1	NM_053004.3	ENSP00000331313.6

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42804 AN: 151928 Hom.: 6552 Cov.: 33

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.282 AC: 42882 AN: 152046 Hom.: 6576 Cov.: 33 AF XY: 0.284 AC XY: 21098 AN XY: 74312

African (AFR) AF: 0.405 AC: 16791 AN: 41446

American (AMR) AF: 0.266 AC: 4071 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 771 AN: 3468

East Asian (EAS) AF: 0.141 AC: 728 AN: 5164

South Asian (SAS) AF: 0.377 AC: 1816 AN: 4812

European-Finnish (FIN) AF: 0.247 AC: 2610 AN: 10578

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15230 AN: 67978

Other (OTH) AF: 0.277 AC: 585 AN: 2110

Alfa AF: 0.247 Hom.: 17090

Bravo AF: 0.287

Asia WGS AF: 0.264 AC: 916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.85
DANN	Benign	0.76
PhyloP100		-1.0
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: rs2073765; hg19: chr22-19800322;