16-23348878-T-C

Variant names:

Variant summary

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

The NM_000336.3(SCNN1B):c.279T>C(p.Pro93Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,613,704 control chromosomes in the GnomAD database, including 294,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 36163 hom., cov: 30)

Exomes 𝑓: 0.58 ( 258772 hom. )

Consequence

SCNN1B
NM_000336.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: -3.32

Publications

27 publications found

Variant links:

Genes affected

SCNN1B (HGNC:10600): (sodium channel epithelial 1 subunit beta) 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 beta subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), and Liddle syndrome. [provided by RefSeq, Apr 2009]

SCNN1B Gene-Disease associations (from GenCC):

Liddle syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
pseudohypoaldosteronism, type IB2, autosomal recessive
Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
bronchiectasis with or without elevated sweat chloride 1
Inheritance: AD, SD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics
pseudohypoaldosteronism, type IB1, autosomal recessive
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
Liddle syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SCNN1B 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 16-23348878-T-C is Benign according to our data. Variant chr16-23348878-T-C is described in ClinVar as Benign. ClinVar VariationId is 165167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1B	NM_000336.3 link	c.279T>C	p.Pro93Pro	synonymous_variant	Exon 2 of 13	ENST00000343070.7	NP_000327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000343070.7 link	c.279T>C	p.Pro93Pro	synonymous_variant	Exon 2 of 13	1	NM_000336.3	ENSP00000345751.2

Frequencies

GnomAD3 genomes

AF:

0.666

AC:

101178

AN:

151872

Hom.:

36106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.905

Gnomad AMI

AF:

0.704

Gnomad AMR

AF:

0.503

Gnomad ASJ

AF:

0.573

Gnomad EAS

AF:

0.985

Gnomad SAS

AF:

0.814

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.552

Gnomad OTH

AF:

0.636

GnomAD2 exomes

AF:

0.621

AC:

155174

AN:

249886

AF XY:

0.629

show subpopulations

Gnomad AFR exome

AF:

0.914

Gnomad AMR exome

AF:

0.435

Gnomad ASJ exome

AF:

0.582

Gnomad EAS exome

AF:

0.984

Gnomad FIN exome

AF:

0.501

Gnomad NFE exome

AF:

0.558

Gnomad OTH exome

AF:

0.600

GnomAD4 exome

AF:

0.584

AC:

853991

AN:

1461714

Hom.:

258772

Cov.:

AF XY:

0.590

AC XY:

428734

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.918

AC:

30730

AN:

33480

American (AMR)

AF:

0.441

AC:

19733

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.578

AC:

15113

AN:

26136

East Asian (EAS)

AF:

0.988

AC:

39241

AN:

39700

South Asian (SAS)

AF:

0.785

AC:

67697

AN:

86256

European-Finnish (FIN)

AF:

0.501

AC:

26748

AN:

53414

Middle Eastern (MID)

AF:

0.716

AC:

4130

AN:

5768

European-Non Finnish (NFE)

AF:

0.552

AC:

613593

AN:

1111854

Other (OTH)

AF:

0.613

AC:

37006

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

19478

38956

58434

77912

97390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17440

34880

52320

69760

87200

<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:

0.666

AC:

101278

AN:

151990

Hom.:

36163

Cov.:

AF XY:

0.668

AC XY:

49640

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.905

AC:

37535

AN:

41464

American (AMR)

AF:

0.502

AC:

7662

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.573

AC:

1990

AN:

3472

East Asian (EAS)

AF:

0.985

AC:

5069

AN:

5146

South Asian (SAS)

AF:

0.814

AC:

3914

AN:

4808

European-Finnish (FIN)

AF:

0.512

AC:

5401

AN:

10558

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.552

AC:

37508

AN:

67956

Other (OTH)

AF:

0.639

AC:

1349

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1483

2967

4450

5934

7417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<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:

0.598

Hom.:

60270

Bravo

AF:

0.674

Asia WGS

AF:

0.896

AC:

3114

AN:

3478

EpiCase

AF:

0.568

EpiControl

AF:

0.581

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Pro93Pro in exon 2 of SCNN1B: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 45.2% (3883/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs238547).

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Oct 21, 2014

Eurofins Ntd Llc (ga)

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

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Pseudohypoaldosteronism, type IB1, autosomal recessive

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 13, 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.

Liddle syndrome 1

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Bronchiectasis with or without elevated sweat chloride 1

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 13, 2018

Illumina Laboratory Services, Illumina

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

0.28

(source)

DANN

Benign

0.58

PhyloP100

-3.3

PromoterAI

-0.022

Neutral

(source)

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