22-19797483-T-C

Variant names:

• chr22-19797483-T-C
• rs2269726
• NM_053004.3:c.732+4518A>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.732+4518A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,072 control chromosomes in the GnomAD database, including 12,408 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 0.40 (12408 hom., cov: 33)
• Consequence: GNB1L NM_053004.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514
• Publications: 12 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB1L	NM_053004.3	c.732+4518A>G		intron_variant	Intron 7 of 7	ENST00000329517.11	NP_443730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB1L	ENST00000329517.11	c.732+4518A>G		intron_variant	Intron 7 of 7	1	NM_053004.3	ENSP00000331313.6
GNB1L	ENST00000403325.5	c.732+4518A>G		intron_variant	Intron 6 of 6	1		ENSP00000385154.1
GNB1L	ENST00000405009.5	c.630+4620A>G		intron_variant	Intron 7 of 7	1		ENSP00000384626.1
GNB1L	ENST00000460402.5	n.700+4518A>G		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60214 AN: 151954 Hom.: 12373 Cov.: 33

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.397 AC: 60299 AN: 152072 Hom.: 12408 Cov.: 33 AF XY: 0.402 AC XY: 29893 AN XY: 74354

African (AFR) AF: 0.448 AC: 18573 AN: 41478

American (AMR) AF: 0.463 AC: 7071 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1486 AN: 3470

East Asian (EAS) AF: 0.577 AC: 2981 AN: 5168

South Asian (SAS) AF: 0.560 AC: 2703 AN: 4830

European-Finnish (FIN) AF: 0.300 AC: 3181 AN: 10592

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.337 AC: 22930 AN: 67948

Other (OTH) AF: 0.408 AC: 859 AN: 2104

Alfa AF: 0.372 Hom.: 18223

Bravo AF: 0.409

Asia WGS AF: 0.525 AC: 1825 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	5.1
DANN	Benign	0.64
PhyloP100		0.51
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: rs2269726; hg19: chr22-19785006; COSMIC: COSV107345257; COSMIC: COSV107345257;