chr14-71964747-A-G
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001204424.2(RGS6):c.-20-25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,496,996 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: 𝑓 0.018 ( 86 hom., cov: 33)
Exomes 𝑓: 0.0019 ( 78 hom. )
Consequence
RGS6
NM_001204424.2 intron
NM_001204424.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.03
Genes affected
RGS6 (HGNC:10002): (regulator of G protein signaling 6) This gene encodes a member of the RGS (regulator of G protein signaling) family of proteins, which are defined by the presence of a RGS domain that confers the GTPase-activating activity of these proteins toward certain G alpha subunits. This protein also belongs to a subfamily of RGS proteins characterized by the presence of DEP and GGL domains, the latter a G beta 5-interacting domain. The RGS proteins negatively regulate G protein signaling, and may modulate neuronal, cardiovascular, lymphocytic activities, and cancer risk. Many alternatively spliced transcript variants encoding different isoforms with long or short N-terminal domains, complete or incomplete GGL domains, and distinct C-terminal domains, have been described for this gene, however, the full-length nature of some of these variants is not known.[provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
This place is a probable branch point but rather VUS (scored 5 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 14-71964747-A-G is Benign according to our data. Variant chr14-71964747-A-G is described in ClinVar as [Benign]. Clinvar id is 1182809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.06 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RGS6 | NM_001204424.2 | c.-20-25A>G | intron_variant | ENST00000553525.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RGS6 | ENST00000553525.6 | c.-20-25A>G | intron_variant | 2 | NM_001204424.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0178 AC: 2704AN: 152132Hom.: 86 Cov.: 33
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GnomAD3 exomes AF: 0.00520 AC: 1182AN: 227252Hom.: 40 AF XY: 0.00358 AC XY: 441AN XY: 123046
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GnomAD4 exome AF: 0.00189 AC: 2545AN: 1344746Hom.: 78 Cov.: 18 AF XY: 0.00165 AC XY: 1111AN XY: 672482
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GnomAD4 genome AF: 0.0178 AC: 2711AN: 152250Hom.: 86 Cov.: 33 AF XY: 0.0171 AC XY: 1273AN XY: 74452
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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:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 06, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
BranchPoint Hunter
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