rs111930830
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_017636.4(TRPM4):c.783G>A(p.Lys261=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,591,836 control chromosomes in the GnomAD database, including 376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.019 ( 49 hom., cov: 30)
Exomes 𝑓: 0.017 ( 327 hom. )
Consequence
TRPM4
NM_017636.4 synonymous
NM_017636.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.20
Genes affected
TRPM4 (HGNC:17993): (transient receptor potential cation channel subfamily M member 4) The protein encoded by this gene is a calcium-activated nonselective ion channel that mediates transport of monovalent cations across membranes, thereby depolarizing the membrane. The activity of the encoded protein increases with increasing intracellular calcium concentration, but this channel does not transport calcium. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
Variant 19-49168723-G-A is Benign according to our data. Variant chr19-49168723-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 220961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49168723-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.2 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0186 (2826/152094) while in subpopulation SAS AF= 0.036 (173/4806). AF 95% confidence interval is 0.0316. There are 49 homozygotes in gnomad4. There are 1449 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 2826 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPM4 | NM_017636.4 | c.783G>A | p.Lys261= | synonymous_variant | 6/25 | ENST00000252826.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPM4 | ENST00000252826.10 | c.783G>A | p.Lys261= | synonymous_variant | 6/25 | 1 | NM_017636.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0186 AC: 2824AN: 151976Hom.: 49 Cov.: 30
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GnomAD3 exomes AF: 0.0216 AC: 4506AN: 208910Hom.: 77 AF XY: 0.0229 AC XY: 2582AN XY: 112710
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GnomAD4 exome AF: 0.0170 AC: 24405AN: 1439742Hom.: 327 Cov.: 33 AF XY: 0.0179 AC XY: 12755AN XY: 714266
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GnomAD4 genome ? AF: 0.0186 AC: 2826AN: 152094Hom.: 49 Cov.: 30 AF XY: 0.0195 AC XY: 1449AN XY: 74348
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 29, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 19, 2023 | - - |
Progressive familial heart block type IB Benign:2
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
TRPM4-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 04, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 01, 2023 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 25, 2015 | This alteration is classified as 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. - |
Computational scores
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Name
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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