rs5723

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001039.4(SCNN1G):c.1947C>G(p.Leu649Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,608,242 control chromosomes in the GnomAD database, including 35,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3530 hom., cov: 32)

Exomes 𝑓: 0.21 ( 32426 hom. )

Consequence

SCNN1G
NM_001039.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.124

Publications

26 publications found

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]

SCNN1G Gene-Disease associations (from GenCC):

Liddle syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
bronchiectasis with or without elevated sweat chloride 3
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
Liddle syndrome 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
pseudohypoaldosteronism, type IB1, autosomal recessive
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

SCNN1G links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 16-23215466-C-G is Benign according to our data. Variant chr16-23215466-C-G is described in ClinVar as Benign. ClinVar VariationId is 165177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.124 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4 link	c.1947C>G	p.Leu649Leu	synonymous_variant	Exon 13 of 13	ENST00000300061.3	NP_001030.2	P51170A5X2V1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061.3 link	c.1947C>G	p.Leu649Leu	synonymous_variant	Exon 13 of 13	1	NM_001039.4	ENSP00000300061.2		P51170

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32178

AN:

152018

Hom.:

3521

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.0603

Gnomad SAS

AF:

0.0742

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.208

GnomAD2 exomes

AF:

0.174

AC:

42641

AN:

244838

AF XY:

0.172

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.0961

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.0626

Gnomad FIN exome

AF:

0.231

Gnomad NFE exome

AF:

0.215

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.205

AC:

298707

AN:

1456106

Hom.:

32426

Cov.:

AF XY:

0.202

AC XY:

146193

AN XY:

724636

show subpopulations

African (AFR)

AF:

0.251

AC:

8418

AN:

33476

American (AMR)

AF:

0.105

AC:

4694

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

6096

AN:

26134

East Asian (EAS)

AF:

0.0558

AC:

2217

AN:

39698

South Asian (SAS)

AF:

0.0845

AC:

7284

AN:

86252

European-Finnish (FIN)

AF:

0.223

AC:

10688

AN:

47916

Middle Eastern (MID)

AF:

0.185

AC:

1066

AN:

5768

European-Non Finnish (NFE)

AF:

0.221

AC:

245790

AN:

1111784

Other (OTH)

AF:

0.206

AC:

12454

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

12733

25466

38200

50933

63666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8280

16560

24840

33120

41400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.212

AC:

32216

AN:

152136

Hom.:

3530

Cov.:

AF XY:

0.208

AC XY:

15504

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.246

AC:

10215

AN:

41506

American (AMR)

AF:

0.162

AC:

2484

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

787

AN:

3472

East Asian (EAS)

AF:

0.0601

AC:

310

AN:

5162

South Asian (SAS)

AF:

0.0742

AC:

358

AN:

4822

European-Finnish (FIN)

AF:

0.231

AC:

2450

AN:

10588

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.220

AC:

14926

AN:

67980

Other (OTH)

AF:

0.214

AC:

453

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1307

2614

3922

5229

6536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.223

Hom.:

720

Bravo

AF:

0.207

Asia WGS

AF:

0.110

AC:

382

AN:

3478

EpiCase

AF:

0.215

EpiControl

AF:

0.209

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Leu649Leu in exon 13 of SCNN1G: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 25.2% (1107/4390) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs5723). -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 22, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 24, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pseudohypoaldosteronism, type IB1, autosomal recessive

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Liddle syndrome 2

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bronchiectasis with or without elevated sweat chloride 3

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.51

(source)

DANN

Benign

0.57

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over