rs765642043
Positions:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The ENST00000306320.10(RETREG1):āc.1026T>Cā(p.Val342=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.000013 ( 0 hom. )
Consequence
RETREG1
ENST00000306320.10 synonymous
ENST00000306320.10 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0610
Genes affected
RETREG1 (HGNC:25964): (reticulophagy regulator 1) The protein encoded by this gene is a cis-Golgi transmembrane protein that may be necessary for the long-term survival of nociceptive and autonomic ganglion neurons. Mutations in this gene are a cause of hereditary sensory and autonomic neuropathy type IIB (HSAN IIB), and this gene may also play a role in susceptibility to vascular dementia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 5-16475209-A-G is Benign according to our data. Variant chr5-16475209-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 538135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.061 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RETREG1 | NM_001034850.3 | c.1026T>C | p.Val342= | synonymous_variant | 9/9 | ENST00000306320.10 | NP_001030022.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RETREG1 | ENST00000306320.10 | c.1026T>C | p.Val342= | synonymous_variant | 9/9 | 1 | NM_001034850.3 | ENSP00000304642 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248806Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135046
GnomAD3 exomes
AF:
AC:
2
AN:
248806
Hom.:
AF XY:
AC XY:
2
AN XY:
135046
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461022Hom.: 0 Cov.: 35 AF XY: 0.00000688 AC XY: 5AN XY: 726858
GnomAD4 exome
AF:
AC:
19
AN:
1461022
Hom.:
Cov.:
35
AF XY:
AC XY:
5
AN XY:
726858
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 28, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at