rs61743044
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_004621.6(TRPC6):c.2115C>T(p.Tyr705=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 1,612,978 control chromosomes in the GnomAD database, including 727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.041 ( 248 hom., cov: 32)
Exomes 𝑓: 0.022 ( 479 hom. )
Consequence
TRPC6
NM_004621.6 synonymous
NM_004621.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.453
Genes affected
TRPC6 (HGNC:12338): (transient receptor potential cation channel subfamily C member 6) The protein encoded by this gene forms a receptor-activated calcium channel in the cell membrane. The channel is activated by diacylglycerol and is thought to be under the control of a phosphatidylinositol second messenger system. Activation of this channel occurs independently of protein kinase C and is not triggered by low levels of intracellular calcium. Defects in this gene are a cause of focal segmental glomerulosclerosis 2 (FSGS2). [provided by RefSeq, Mar 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 11-101472227-G-A is Benign according to our data. Variant chr11-101472227-G-A is described in ClinVar as [Benign]. Clinvar id is 259458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-101472227-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.453 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0997 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPC6 | NM_004621.6 | c.2115C>T | p.Tyr705= | synonymous_variant | 8/13 | ENST00000344327.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPC6 | ENST00000344327.8 | c.2115C>T | p.Tyr705= | synonymous_variant | 8/13 | 1 | NM_004621.6 | P1 | |
TRPC6 | ENST00000360497.4 | c.1950C>T | p.Tyr650= | synonymous_variant | 7/12 | 1 | |||
TRPC6 | ENST00000348423.8 | c.1767C>T | p.Tyr589= | synonymous_variant | 6/11 | 1 | |||
TRPC6 | ENST00000532133.5 | c.1881C>T | p.Tyr627= | synonymous_variant | 7/12 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0411 AC: 6245AN: 152062Hom.: 248 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
6245
AN:
152062
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0200 AC: 4996AN: 250108Hom.: 140 AF XY: 0.0182 AC XY: 2458AN XY: 135220
GnomAD3 exomes
AF:
AC:
4996
AN:
250108
Hom.:
AF XY:
AC XY:
2458
AN XY:
135220
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: 0.0216 AC: 31622AN: 1460798Hom.: 479 Cov.: 31 AF XY: 0.0208 AC XY: 15110AN XY: 726706
GnomAD4 exome
AF:
AC:
31622
AN:
1460798
Hom.:
Cov.:
31
AF XY:
AC XY:
15110
AN XY:
726706
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 ? AF: 0.0411 AC: 6258AN: 152180Hom.: 248 Cov.: 32 AF XY: 0.0388 AC XY: 2886AN XY: 74384
GnomAD4 genome
?
AF:
AC:
6258
AN:
152180
Hom.:
Cov.:
32
AF XY:
AC XY:
2886
AN XY:
74384
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
30
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 12, 2020 | - - |
Focal segmental glomerulosclerosis 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 15, 2017 | - - |
Focal segmental glomerulosclerosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Oct 18, 2021 | - - |
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