rs5739
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001039.4(SCNN1G):c.636C>T(p.Ser212=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 1,613,838 control chromosomes in the GnomAD database, including 487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.018 ( 52 hom., cov: 31)
Exomes 𝑓: 0.022 ( 435 hom. )
Consequence
SCNN1G
NM_001039.4 synonymous
NM_001039.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.12
Genes affected
SCNN1G (HGNC:10602): (sodium channel epithelial 1 subunit gamma) Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in many organs. These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. This gene encodes the gamma subunit, and mutations in this gene have been associated with Liddle syndrome. [provided by RefSeq, Apr 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 16-23192369-C-T is Benign according to our data. Variant chr16-23192369-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 178805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23192369-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-3.12 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0176 (2673/152272) while in subpopulation NFE AF= 0.0264 (1798/68022). AF 95% confidence interval is 0.0254. There are 52 homozygotes in gnomad4. There are 1305 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 52 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCNN1G | NM_001039.4 | c.636C>T | p.Ser212= | synonymous_variant | 4/13 | ENST00000300061.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCNN1G | ENST00000300061.3 | c.636C>T | p.Ser212= | synonymous_variant | 4/13 | 1 | NM_001039.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0176 AC: 2676AN: 152154Hom.: 52 Cov.: 31
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GnomAD3 exomes AF: 0.0192 AC: 4835AN: 251460Hom.: 74 AF XY: 0.0196 AC XY: 2669AN XY: 135900
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GnomAD4 exome AF: 0.0216 AC: 31615AN: 1461566Hom.: 435 Cov.: 32 AF XY: 0.0214 AC XY: 15542AN XY: 727092
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GnomAD4 genome ? AF: 0.0176 AC: 2673AN: 152272Hom.: 52 Cov.: 31 AF XY: 0.0175 AC XY: 1305AN XY: 74452
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Ser212Ser in exon 4 of SCNN1G: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 2.4% (207/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs5739). - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 16, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 16, 2020 | - - |
Liddle syndrome 2 Benign:1
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. - |
Autosomal recessive pseudohypoaldosteronism type 1 Benign:1
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. - |
Computational scores
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Name
Calibrated prediction
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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