rs5748427

Variant names:

• chr22-19787764-A-G
• rs5748427
• NM_053004.3:c.*945T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 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.*945T>C		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.*945T>C		3_prime_UTR	Exon 8 of 8	ENSP00000331313.6	Q9BYB4-1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.278 AC: 25 AN: 90

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.535 AC: 22180 AN: 41490

American (AMR) AF: 0.475 AC: 7270 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1540 AN: 3466

East Asian (EAS) AF: 0.575 AC: 2970 AN: 5166

South Asian (SAS) AF: 0.561 AC: 2703 AN: 4822

European-Finnish (FIN) AF: 0.300 AC: 3173 AN: 10584

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23069 AN: 67990

Other (OTH) AF: 0.426 AC: 900 AN: 2112

Alfa AF: 0.385 Hom.: 33140

Bravo AF: 0.440

Asia WGS AF: 0.532 AC: 1847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.20
PhyloP100		-0.080
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: rs5748427; hg19: chr22-19775287;