rs5748427

Positions:

• chr22-19787764-A-G
• chr22-19787764-A-T

Variant summary

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

The NM_053004.3(GNB1L):​c.*945T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,226 control chromosomes in the GnomAD database, including 14,375 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 0.42 (14370 hom., cov: 34)
  • Exomes 𝑓: 0.30 (5 hom.)
• Consequence: GNB1L NM_053004.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNB1L	NM_053004.3	c.*945T>C		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	c.*945T>C		3_prime_UTR_variant	8/8	1	NM_053004.3	ENSP00000331313.6

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64241 AN: 152008 Hom.: 14334 Cov.: 34

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.428

GnomAD4 exome AF: 0.300 AC: 30 AN: 100 Hom.: 5 Cov.: 0 AF XY: 0.292 AC XY: 21 AN XY: 72

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.423 AC: 64331 AN: 152126 Hom.: 14370 Cov.: 34 AF XY: 0.427 AC XY: 31786 AN XY: 74372

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.426

Alfa AF: 0.376 Hom.: 18517

Bravo AF: 0.440

Asia WGS AF: 0.532 AC: 1847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.20

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: rs5748427; hg19: chr22-19775287;