rs5748425

Positions:

• chr22-19787520-G-A
• chr22-19787520-G-C

Variant summary

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

The NM_053004.3(GNB1L):​c.*1189C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,510 control chromosomes in the GnomAD database, including 4,743 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 0.24 (4737 hom., cov: 33)
  • Exomes 𝑓: 0.18 (6 hom.)
• Consequence: GNB1L NM_053004.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNB1L	NM_053004.3	c.*1189C>T		3_prime_UTR_variant	8/8	ENST00000329517.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB1L	ENST00000329517.11	c.*1189C>T		3_prime_UTR_variant	8/8	1	NM_053004.3	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36975 AN: 152138 Hom.: 4723 Cov.: 33

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0982

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.181 AC: 46 AN: 254 Hom.: 6 Cov.: 0 AF XY: 0.180 AC XY: 35 AN XY: 194

Gnomad4 AFR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.243 AC: 37034 AN: 152256 Hom.: 4737 Cov.: 33 AF XY: 0.245 AC XY: 18248 AN XY: 74434

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.0982

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.261

Alfa AF: 0.227 Hom.: 5423

Bravo AF: 0.244

Asia WGS AF: 0.221 AC: 768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.46

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: rs5748425; hg19: chr22-19775043;