rs5993835

chr22-19807489-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053004.3(GNB1L):c.418-732T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 151,476 control chromosomes in the GnomAD database, including 418 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 0.048 (418 hom., cov: 33)
• Consequence: GNB1L NM_053004.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNB1L	NM_053004.3	c.418-732T>C		intron_variant		ENST00000329517.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB1L	ENST00000329517.11	c.418-732T>C		intron_variant		1	NM_053004.3	P1

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7227 AN: 151358 Hom.: 412 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.00376

Gnomad EAS AF: 0.0540

Gnomad SAS AF: 0.0902

Gnomad FIN AF: 0.00529

Gnomad MID AF: 0.0353

Gnomad NFE AF: 0.00702

Gnomad OTH AF: 0.0343

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

GnomAD4 genome AF: 0.0479 AC: 7256 AN: 151476 Hom.: 418 Cov.: 33 AF XY: 0.0483 AC XY: 3573 AN XY: 74028

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0248

Gnomad4 ASJ AF: 0.00376

Gnomad4 EAS AF: 0.0543

Gnomad4 SAS AF: 0.0901

Gnomad4 FIN AF: 0.00529

Gnomad4 NFE AF: 0.00702

Gnomad4 OTH AF: 0.0339

Alfa AF: 0.0269 Hom.: 53

Bravo AF: 0.0522

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.13
Dann	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs5993835; hg19: chr22-19795012;