chr8-103500928-C-A
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_001348484.3(RIMS2):c.42C>A(p.Ile14=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,608,064 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0071 ( 21 hom., cov: 32)
Exomes 𝑓: 0.00062 ( 7 hom. )
Consequence
RIMS2
NM_001348484.3 synonymous
NM_001348484.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.339
Genes affected
RIMS2 (HGNC:17283): (regulating synaptic membrane exocytosis 2) The protein encoded by this gene is a presynaptic protein that interacts with RAB3, a protein important for normal neurotransmitter release. The encoded protein can also bind several other synaptic proteins, including UNC-13 homolog B, ELKS/Rab6-interacting/CAST family member 1, and synaptotagmin 1. This protein is involved in synaptic membrane exocytosis. Polymorphisms in this gene have been associated with degenerative lumbar scoliosis. [provided by RefSeq, Feb 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
?
Variant 8-103500928-C-A is Benign according to our data. Variant chr8-103500928-C-A is described in ClinVar as [Benign]. Clinvar id is 790611.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00709 (1080/152230) while in subpopulation AFR AF= 0.0245 (1019/41560). AF 95% confidence interval is 0.0233. There are 21 homozygotes in gnomad4. There are 484 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 21 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RIMS2 | NM_001348484.3 | c.42C>A | p.Ile14= | synonymous_variant | 1/30 | ENST00000696799.1 | |
LOC105375690 | NR_145698.1 | n.115+868G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RIMS2 | ENST00000696799.1 | c.42C>A | p.Ile14= | synonymous_variant | 1/30 | NM_001348484.3 | A1 | ||
ENST00000523422.1 | n.277+472G>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00710 AC: 1080AN: 152112Hom.: 21 Cov.: 32
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GnomAD3 exomes AF: 0.00161 AC: 388AN: 240944Hom.: 6 AF XY: 0.00118 AC XY: 156AN XY: 132126
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GnomAD4 exome AF: 0.000617 AC: 898AN: 1455834Hom.: 7 Cov.: 31 AF XY: 0.000492 AC XY: 356AN XY: 724178
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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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