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GeneBe

rs5734

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001039.4(SCNN1G):ā€‹c.387T>Cā€‹(p.Tyr129=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,613,870 control chromosomes in the GnomAD database, including 76,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.27 ( 6188 hom., cov: 32)
Exomes š‘“: 0.31 ( 70206 hom. )

Consequence

SCNN1G
NM_001039.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.39
Variant links:
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
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-23189440-T-C is Benign according to our data. Variant chr16-23189440-T-C is described in ClinVar as [Benign]. Clinvar id is 165172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23189440-T-C is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.39 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCNN1GNM_001039.4 linkuse as main transcriptc.387T>C p.Tyr129= synonymous_variant 3/13 ENST00000300061.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCNN1GENST00000300061.3 linkuse as main transcriptc.387T>C p.Tyr129= synonymous_variant 3/131 NM_001039.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.272
AC:
41404
AN:
152000
Hom.:
6165
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.157
Gnomad AMI
AF:
0.315
Gnomad AMR
AF:
0.356
Gnomad ASJ
AF:
0.295
Gnomad EAS
AF:
0.180
Gnomad SAS
AF:
0.267
Gnomad FIN
AF:
0.362
Gnomad MID
AF:
0.297
Gnomad NFE
AF:
0.316
Gnomad OTH
AF:
0.276
GnomAD3 exomes
AF:
0.309
AC:
77645
AN:
251300
Hom.:
12885
AF XY:
0.305
AC XY:
41377
AN XY:
135852
show subpopulations
Gnomad AFR exome
AF:
0.157
Gnomad AMR exome
AF:
0.436
Gnomad ASJ exome
AF:
0.305
Gnomad EAS exome
AF:
0.172
Gnomad SAS exome
AF:
0.270
Gnomad FIN exome
AF:
0.367
Gnomad NFE exome
AF:
0.314
Gnomad OTH exome
AF:
0.312
GnomAD4 exome
AF:
0.306
AC:
447170
AN:
1461752
Hom.:
70206
Cov.:
42
AF XY:
0.305
AC XY:
221919
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.148
Gnomad4 AMR exome
AF:
0.431
Gnomad4 ASJ exome
AF:
0.307
Gnomad4 EAS exome
AF:
0.162
Gnomad4 SAS exome
AF:
0.271
Gnomad4 FIN exome
AF:
0.369
Gnomad4 NFE exome
AF:
0.311
Gnomad4 OTH exome
AF:
0.304
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.273
AC:
41478
AN:
152118
Hom.:
6188
Cov.:
32
AF XY:
0.274
AC XY:
20398
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.158
Gnomad4 AMR
AF:
0.356
Gnomad4 ASJ
AF:
0.295
Gnomad4 EAS
AF:
0.180
Gnomad4 SAS
AF:
0.268
Gnomad4 FIN
AF:
0.362
Gnomad4 NFE
AF:
0.316
Gnomad4 OTH
AF:
0.275
Alfa
AF:
0.311
Hom.:
4396
Bravo
AF:
0.269
Asia WGS
AF:
0.274
AC:
950
AN:
3478
EpiCase
AF:
0.306
EpiControl
AF:
0.307

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsJul 24, 2017- -
Benign, criteria provided, single submitterclinical testingInvitaeJan 30, 2024- -
not specified Benign:2
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineFeb 21, 2013Tyr129Tyr in exon 3 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 32.1% (2759/8600) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs5734). -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Liddle syndrome 2 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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 submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.036
DANN
Benign
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs5734; hg19: chr16-23200761; COSMIC: COSV55597758; API