16-23367958-C-T

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.879C>T(p.Phe293Phe) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0546 in 1,610,998 control chromosomes in the GnomAD database, including 3,889 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.098 ( 1203 hom., cov: 34)

Exomes 𝑓: 0.050 ( 2686 hom. )

Consequence

SCNN1B
NM_000336.3 splice_region, synonymous

Scores

Splicing: ADA: 0.0004873

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.72

Publications

12 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=-0.72).

BP6

Variant 16-23367958-C-T is Benign according to our data. Variant chr16-23367958-C-T is described in ClinVar as Benign. ClinVar VariationId is 178802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.72 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1B	NM_000336.3 link	c.879C>T	p.Phe293Phe	splice_region_variant, synonymous_variant	Exon 5 of 13	ENST00000343070.7	NP_000327.2	P51168-1B2R812

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000343070.7 link	c.879C>T	p.Phe293Phe	splice_region_variant, synonymous_variant	Exon 5 of 13	1	NM_000336.3	ENSP00000345751.2		P51168-1

Frequencies

GnomAD3 genomes

AF:

0.0976

AC:

14846

AN:

152096

Hom.:

1201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0567

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.0940

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0509

Gnomad OTH

AF:

0.0823

GnomAD2 exomes

AF:

0.0563

AC:

14160

AN:

251486

AF XY:

0.0522

show subpopulations

Gnomad AFR exome

AF:

0.226

Gnomad AMR exome

AF:

0.0384

Gnomad ASJ exome

AF:

0.0480

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.0897

Gnomad NFE exome

AF:

0.0520

Gnomad OTH exome

AF:

0.0583

GnomAD4 exome

AF:

0.0501

AC:

73153

AN:

1458784

Hom.:

2686

Cov.:

AF XY:

0.0489

AC XY:

35502

AN XY:

725988

show subpopulations

African (AFR)

AF:

0.231

AC:

7711

AN:

33352

American (AMR)

AF:

0.0399

AC:

1783

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0486

AC:

1270

AN:

26116

East Asian (EAS)

AF:

0.000101

AC:

AN:

39684

South Asian (SAS)

AF:

0.0157

AC:

1351

AN:

86196

European-Finnish (FIN)

AF:

0.0835

AC:

4462

AN:

53416

Middle Eastern (MID)

AF:

0.0744

AC:

429

AN:

5768

European-Non Finnish (NFE)

AF:

0.0476

AC:

52814

AN:

1109246

Other (OTH)

AF:

0.0552

AC:

3329

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

3452

6904

10355

13807

17259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1970

3940

5910

7880

9850

<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:

0.0976

AC:

14862

AN:

152214

Hom.:

1203

Cov.:

AF XY:

0.0969

AC XY:

7213

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.219

AC:

9076

AN:

41500

American (AMR)

AF:

0.0568

AC:

868

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0493

AC:

171

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5192

South Asian (SAS)

AF:

0.0118

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0940

AC:

995

AN:

10590

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0509

AC:

3465

AN:

68026

Other (OTH)

AF:

0.0814

AC:

172

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

653

1305

1958

2610

3263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<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:

0.0652

Hom.:

1564

Bravo

AF:

0.101

EpiCase

AF:

0.0546

EpiControl

AF:

0.0535

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Sep 12, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 26, 2020

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Oct 18, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Phe293Phe in exon 05 of SCNN1B: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not predicted to alter splicing (0/5 programs). It has been identified in 20% (915/4394) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs250563). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pseudohypoaldosteronism, type IB1, autosomal recessive

Benign:1

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:1

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:1

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

-0.72

CADD

Benign

1.3

(source)

DANN

Benign

0.65

PhyloP100

-1.7

Mutation Taster

=76/24

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00049

dbscSNV1_RF

Benign

0.28

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