chr22-19791614-G-T

Variant names:

• chr22-19791614-G-T
• rs5746834
• NM_053004.3:c.733-2654C>A

Variant summary

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

The NM_053004.3(GNB1L):​c.733-2654C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,156 control chromosomes in the GnomAD database, including 3,910 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 0.22 (3910 hom., cov: 32)
• Consequence: GNB1L NM_053004.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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 (SAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB1L	NM_053004.3	c.733-2654C>A		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.733-2654C>A		intron_variant	Intron 7 of 7	1	NM_053004.3	ENSP00000331313.6
GNB1L	ENST00000403325.5	c.733-2654C>A		intron_variant	Intron 6 of 6	1		ENSP00000385154.1
GNB1L	ENST00000405009.5	c.631-2988C>A		intron_variant	Intron 7 of 7	1		ENSP00000384626.1
GNB1L	ENST00000460402.5	n.701-2654C>A		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33321 AN: 152038 Hom.: 3891 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0983

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.219 AC: 33396 AN: 152156 Hom.: 3910 Cov.: 32 AF XY: 0.222 AC XY: 16498 AN XY: 74402

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.0984

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.231

Alfa AF: 0.203 Hom.: 4365

Bravo AF: 0.221

Asia WGS AF: 0.223 AC: 774 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	0.019
DANN	Benign	0.58

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: rs5746834; hg19: chr22-19779137;