rs1799980

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000336.3(SCNN1B):c.1325G>T(p.Gly442Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00684 in 1,614,172 control chromosomes in the GnomAD database, including 640 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G442S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.036 ( 345 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 295 hom. )

Consequence

SCNN1B
NM_000336.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.170

Publications

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

SCNN1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015711784).

BP6

Variant 16-23377219-G-T is Benign according to our data. Variant chr16-23377219-G-T is described in ClinVar as Benign. ClinVar VariationId is 178804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000336.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1B	NM_000336.3	MANE Select	c.1325G>T	p.Gly442Val	missense	Exon 9 of 13	NP_000327.2	B2R812
	SCNN1B	NM_001410900.1		c.1217G>T	p.Gly406Val	missense	Exon 8 of 12	NP_001397829.1	H3BQ95

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCNN1B	ENST00000343070.7	TSL:1 MANE Select	c.1325G>T	p.Gly442Val	missense	Exon 9 of 13	ENSP00000345751.2	P51168-1
SCNN1B	ENST00000307331.9	TSL:5	c.1460G>T	p.Gly487Val	missense	Exon 10 of 14	ENSP00000302874.5	P51168-2
SCNN1B	ENST00000962247.1		c.1421G>T	p.Gly474Val	missense	Exon 9 of 13	ENSP00000632306.1

Frequencies

GnomAD3 genomes

AF:

0.0363

AC:

5528

AN:

152196

Hom.:

345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0159

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0277

GnomAD2 exomes

AF:

0.00985

AC:

2475

AN:

251342

AF XY:

0.00691

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.00735

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000396

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00376

AC:

5495

AN:

1461858

Hom.:

295

Cov.:

AF XY:

0.00320

AC XY:

2326

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.128

AC:

4291

AN:

33480

American (AMR)

AF:

0.00762

AC:

341

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000995

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000313

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00589

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000235

AC:

261

AN:

1112004

Other (OTH)

AF:

0.00851

AC:

514

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

333

665

998

1330

1663

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

264

396

528

660

<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:

0.0364

AC:

5550

AN:

152314

Hom.:

345

Cov.:

AF XY:

0.0348

AC XY:

2592

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.125

AC:

5203

AN:

41546

American (AMR)

AF:

0.0159

AC:

243

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000500

AC:

AN:

68034

Other (OTH)

AF:

0.0274

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

251

501

752

1002

1253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0150

Hom.:

316

Bravo

AF:

0.0412

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.129

AC:

565

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0123

AC:

1491

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (3)

Bronchiectasis with or without elevated sweat chloride 1 (1)

Liddle syndrome 1 (1)

Pseudohypoaldosteronism, type IB1, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.95

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.13

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

0.17

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.44

REVEL

Benign

0.14

Sift

Benign

0.085

Sift4G

Benign

0.23

Polyphen

0.040

Vest4

0.11

MPC

0.22

ClinPred

0.0041

GERP RS

-5.5

Varity_R

0.089

gMVP

0.29

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over