chr22-19788883-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_053004.3(GNB1L):c.810C>T(p.Thr270=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,612,894 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0019 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0024 ( 33 hom. )
Consequence
GNB1L
NM_053004.3 synonymous
NM_053004.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.96
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 22-19788883-G-A is Benign according to our data. Variant chr22-19788883-G-A is described in ClinVar as [Benign]. Clinvar id is 711009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-4.96 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00188 (286/152352) while in subpopulation SAS AF= 0.0205 (99/4828). AF 95% confidence interval is 0.0172. There are 2 homozygotes in gnomad4. There are 171 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNB1L | NM_053004.3 | c.810C>T | p.Thr270= | synonymous_variant | 8/8 | ENST00000329517.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNB1L | ENST00000329517.11 | c.810C>T | p.Thr270= | synonymous_variant | 8/8 | 1 | NM_053004.3 | P1 | |
GNB1L | ENST00000403325.5 | c.810C>T | p.Thr270= | synonymous_variant | 7/7 | 1 | P1 | ||
GNB1L | ENST00000405009.5 | c.631-257C>T | intron_variant | 1 | |||||
GNB1L | ENST00000460402.5 | n.778C>T | non_coding_transcript_exon_variant | 6/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00187 AC: 285AN: 152234Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.00355 AC: 881AN: 248228Hom.: 11 AF XY: 0.00414 AC XY: 559AN XY: 134862
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GnomAD4 exome AF: 0.00237 AC: 3455AN: 1460542Hom.: 33 Cov.: 32 AF XY: 0.00277 AC XY: 2012AN XY: 726594
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
GNB1L-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 20, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at