rs200696108
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_021629.4(GNB4):āc.243T>Cā(p.Ile81=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000797 in 1,594,112 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00037 ( 0 hom., cov: 32)
Exomes š: 0.000049 ( 2 hom. )
Consequence
GNB4
NM_021629.4 synonymous
NM_021629.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.644
Genes affected
GNB4 (HGNC:20731): (G protein subunit beta 4) Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. [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=-0.49).
BP6
?
Variant 3-179416517-A-G is Benign according to our data. Variant chr3-179416517-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 540923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.644 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000368 (56/152320) while in subpopulation AFR AF= 0.00127 (53/41578). AF 95% confidence interval is 0.001. There are 0 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 56 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNB4 | NM_021629.4 | c.243T>C | p.Ile81= | synonymous_variant | 5/10 | ENST00000232564.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNB4 | ENST00000232564.8 | c.243T>C | p.Ile81= | synonymous_variant | 5/10 | 1 | NM_021629.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000375 AC: 57AN: 152202Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000104 AC: 25AN: 240726Hom.: 0 AF XY: 0.0000614 AC XY: 8AN XY: 130318
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GnomAD4 exome AF: 0.0000492 AC: 71AN: 1441792Hom.: 2 Cov.: 26 AF XY: 0.0000418 AC XY: 30AN XY: 717812
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GnomAD4 genome ? AF: 0.000368 AC: 56AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25AN XY: 74496
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Charcot-Marie-Tooth disease dominant intermediate F Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 21, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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