rs4819523

Variant names:

• chr22-19810549-G-C
• rs4819523
• NM_053004.3:c.417+1736C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053004.3(GNB1L):​c.417+1736C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,058 control chromosomes in the GnomAD database, including 18,666 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 0.48 (18666 hom., cov: 33)
• Consequence: GNB1L NM_053004.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB1L	NM_053004.3	c.417+1736C>G		intron_variant	Intron 5 of 7	ENST00000329517.11	NP_443730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB1L	ENST00000329517.11	c.417+1736C>G		intron_variant	Intron 5 of 7	1	NM_053004.3	ENSP00000331313.6

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73134 AN: 151940 Hom.: 18617 Cov.: 33

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.482 AC: 73242 AN: 152058 Hom.: 18666 Cov.: 33 AF XY: 0.486 AC XY: 36168 AN XY: 74356

African (AFR) AF: 0.643 AC: 26689 AN: 41482

American (AMR) AF: 0.514 AC: 7861 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3470

East Asian (EAS) AF: 0.432 AC: 2225 AN: 5150

South Asian (SAS) AF: 0.593 AC: 2857 AN: 4816

European-Finnish (FIN) AF: 0.415 AC: 4390 AN: 10574

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26409 AN: 67958

Other (OTH) AF: 0.473 AC: 999 AN: 2110

Alfa AF: 0.439 Hom.: 1935

Bravo AF: 0.498

Asia WGS AF: 0.516 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.68
DANN	Benign	0.43
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4819523; hg19: chr22-19798072;