rs5748425

Variant names:

• chr22-19787520-G-A
• rs5748425
• NM_053004.3:c.*1189C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053004.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB1L	NM_053004.3	MANE Select	c.*1189C>T		3_prime_UTR	Exon 8 of 8	NP_443730.1	Q9BYB4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB1L	ENST00000329517.11	TSL:1 MANE Select	c.*1189C>T		3_prime_UTR	Exon 8 of 8	ENSP00000331313.6	Q9BYB4-1

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

African (AFR) AF: 0.100 AC: 1 AN: 10

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 4 AN: 8

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.175 AC: 36 AN: 206

Other (OTH) AF: 0.188 AC: 3 AN: 16

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

African (AFR) AF: 0.291 AC: 12082 AN: 41540

American (AMR) AF: 0.232 AC: 3553 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3470

East Asian (EAS) AF: 0.0982 AC: 508 AN: 5172

South Asian (SAS) AF: 0.336 AC: 1621 AN: 4830

European-Finnish (FIN) AF: 0.240 AC: 2548 AN: 10606

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15150 AN: 68016

Other (OTH) AF: 0.261 AC: 551 AN: 2114

Alfa AF: 0.230 Hom.: 7063

Bravo AF: 0.244

Asia WGS AF: 0.221 AC: 768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.46
PhyloP100		0.27
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: rs5748425; hg19: chr22-19775043;