rs371262137
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_004621.6(TRPC6):c.1293+6_1293+18del variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000907 in 1,613,890 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0049 ( 8 hom., cov: 33)
Exomes 𝑓: 0.00049 ( 5 hom. )
Consequence
TRPC6
NM_004621.6 splice_donor_region, intron
NM_004621.6 splice_donor_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.94
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 11-101488918-CCAGGCTTCACATA-C is Benign according to our data. Variant chr11-101488918-CCAGGCTTCACATA-C is described in ClinVar as [Benign]. Clinvar id is 586845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00491 (748/152264) while in subpopulation AFR AF= 0.0172 (713/41536). AF 95% confidence interval is 0.0161. There are 8 homozygotes in gnomad4. There are 346 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 747 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPC6 | NM_004621.6 | c.1293+6_1293+18del | splice_donor_region_variant, intron_variant | ENST00000344327.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPC6 | ENST00000344327.8 | c.1293+6_1293+18del | splice_donor_region_variant, intron_variant | 1 | NM_004621.6 | P1 | |||
TRPC6 | ENST00000348423.8 | c.946-5766_946-5754del | intron_variant | 1 | |||||
TRPC6 | ENST00000360497.4 | c.1128+2625_1128+2637del | intron_variant | 1 | |||||
TRPC6 | ENST00000532133.5 | c.1293+6_1293+18del | splice_donor_region_variant, intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00491 AC: 747AN: 152146Hom.: 8 Cov.: 33
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GnomAD3 exomes AF: 0.00121 AC: 304AN: 250914Hom.: 2 AF XY: 0.000899 AC XY: 122AN XY: 135674
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GnomAD4 exome AF: 0.000490 AC: 716AN: 1461626Hom.: 5 AF XY: 0.000396 AC XY: 288AN XY: 727130
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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 | clinical testing | Invitae | Jan 12, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 29, 2017 | - - |
Computational scores
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at