dbSNP rs13306628: SCNN1B:p.Thr594Thr (chr16-23380660-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000336.3(SCNN1B):c.1782G>A(p.Thr594Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00091 in 1,612,708 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00092 ( 6 hom. )

Consequence

SCNN1B
NM_000336.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.568

Publications

1 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-23380660-G-A is Benign according to our data. Variant chr16-23380660-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.568 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000808 (123/152266) while in subpopulation EAS AF = 0.00969 (50/5160). AF 95% confidence interval is 0.00755. There are 0 homozygotes in GnomAd4. There are 71 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 6 AR,AD,SD gene

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.1782G>A	p.Thr594Thr	synonymous	Exon 13 of 13	NP_000327.2	B2R812
	SCNN1B	NM_001410900.1		c.1674G>A	p.Thr558Thr	synonymous	Exon 12 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.1782G>A	p.Thr594Thr	synonymous	Exon 13 of 13	ENSP00000345751.2	P51168-1
SCNN1B	ENST00000307331.9	TSL:5	c.1917G>A	p.Thr639Thr	synonymous	Exon 14 of 14	ENSP00000302874.5	P51168-2
SCNN1B	ENST00000962247.1		c.1878G>A	p.Thr626Thr	synonymous	Exon 13 of 13	ENSP00000632306.1

Frequencies

GnomAD3 genomes

AF:

0.000808

AC:

123

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00967

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00145

AC:

360

AN:

247678

AF XY:

0.00162

show subpopulations

Gnomad AFR exome

AF:

0.000192

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00422

Gnomad EAS exome

AF:

0.00923

Gnomad FIN exome

AF:

0.0000939

Gnomad NFE exome

AF:

0.000565

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000920

AC:

1344

AN:

1460442

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

732

AN XY:

726482

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33464

American (AMR)

AF:

0.000157

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00449

AC:

117

AN:

26080

East Asian (EAS)

AF:

0.00706

AC:

280

AN:

39682

South Asian (SAS)

AF:

0.00281

AC:

242

AN:

86192

European-Finnish (FIN)

AF:

0.000227

AC:

AN:

52882

Middle Eastern (MID)

AF:

0.00284

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.000471

AC:

523

AN:

1111510

Other (OTH)

AF:

0.00230

AC:

139

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

179

268

358

447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.000808

AC:

123

AN:

152266

Hom.:

Cov.:

AF XY:

0.000954

AC XY:

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41570

American (AMR)

AF:

0.000131

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.00969

AC:

AN:

5160

South Asian (SAS)

AF:

0.00270

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

68004

Other (OTH)

AF:

0.00142

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000955

Hom.:

Bravo

AF:

0.000740

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000889

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bronchiectasis with or without elevated sweat chloride 1 (1)

Liddle syndrome 1 (1)

not provided (1)

not specified (1)

Pseudohypoaldosteronism, type IB1, autosomal recessive (1)

SCNN1B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.94

(source)

DANN

Benign

0.50

PhyloP100

-0.57

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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