rs78051297
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_017636.4(TRPM4):c.448+6C>T 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 0.00174 in 1,599,858 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0094 ( 20 hom., cov: 32)
Exomes 𝑓: 0.00094 ( 26 hom. )
Consequence
TRPM4
NM_017636.4 splice_donor_region, intron
NM_017636.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00002646
2
Clinical Significance
Conservation
PhyloP100: 0.0210
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 19-49168103-C-T is Benign according to our data. Variant chr19-49168103-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49168103-C-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00935 (1424/152260) while in subpopulation AFR AF= 0.0321 (1334/41534). AF 95% confidence interval is 0.0307. There are 20 homozygotes in gnomad4. There are 668 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1424 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPM4 | NM_017636.4 | c.448+6C>T | splice_donor_region_variant, intron_variant | ENST00000252826.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPM4 | ENST00000252826.10 | c.448+6C>T | splice_donor_region_variant, intron_variant | 1 | NM_017636.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00929 AC: 1414AN: 152142Hom.: 20 Cov.: 32
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GnomAD3 exomes AF: 0.00238 AC: 564AN: 236968Hom.: 11 AF XY: 0.00171 AC XY: 222AN XY: 129614
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GnomAD4 exome AF: 0.000943 AC: 1365AN: 1447598Hom.: 26 Cov.: 33 AF XY: 0.000764 AC XY: 550AN XY: 719866
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GnomAD4 genome AF: 0.00935 AC: 1424AN: 152260Hom.: 20 Cov.: 32 AF XY: 0.00897 AC XY: 668AN XY: 74436
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Progressive familial heart block type IB Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 21, 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at