rs5746832

Positions:

• chr22-19783667-G-A

Variant summary

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

The NM_053004.3(GNB1L):​c.*5042C>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 0.439 in 159,142 control chromosomes in the GnomAD database, including 15,651 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 0.44 (14951 hom., cov: 33)
  • Exomes 𝑓: 0.43 (700 hom.)
• Consequence: GNB1L NM_053004.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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 (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNB1L	NM_053004.3	c.*5042C>T		3_prime_UTR_variant	8/8	ENST00000329517.11	NP_443730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNB1L	ENST00000329517.11	c.*5042C>T		3_prime_UTR_variant	8/8	1	NM_053004.3	ENSP00000331313	P1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66790 AN: 152030 Hom.: 14929 Cov.: 33

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.428 AC: 2991 AN: 6994 Hom.: 700 Cov.: 0 AF XY: 0.425 AC XY: 1535 AN XY: 3616

Gnomad4 AFR exome AF: 0.429

Gnomad4 AMR exome AF: 0.501

Gnomad4 ASJ exome AF: 0.581

Gnomad4 EAS exome AF: 0.472

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.418

GnomAD4 genome AF: 0.439 AC: 66865 AN: 152148 Hom.: 14951 Cov.: 33 AF XY: 0.441 AC XY: 32788 AN XY: 74386

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.462

Alfa AF: 0.430 Hom.: 1813

Bravo AF: 0.450

Asia WGS AF: 0.467 AC: 1624 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	2.7
DANN	Benign	0.53

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: rs5746832; hg19: chr22-19771190;