chr16-23380404-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000336.3(SCNN1B):c.1543-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00822 in 1,614,002 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 56 hom. )

Consequence

SCNN1B
NM_000336.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.164

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, 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-23380404-C-T is Benign according to our data. Variant chr16-23380404-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00704 (1072/152330) while in subpopulation NFE AF = 0.0103 (700/68024). AF 95% confidence interval is 0.00966. There are 10 homozygotes in GnomAd4. There are 518 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR,AD,SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1B	NM_000336.3 link	c.1543-17C>T		intron_variant	Intron 12 of 12	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.1543-17C>T		intron_variant	Intron 12 of 12	1	NM_000336.3	ENSP00000345751.2		P51168-1

Frequencies

GnomAD3 genomes

AF:

0.00705

AC:

1073

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.0615

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00642

AC:

1611

AN:

250898

AF XY:

0.00649

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0132

Gnomad NFE exome

AF:

0.00974

Gnomad OTH exome

AF:

0.00669

GnomAD4 exome

AF:

0.00835

AC:

12201

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00830

AC XY:

6038

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.00134

AC:

AN:

33480

American (AMR)

AF:

0.00362

AC:

162

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00310

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00108

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0125

AC:

665

AN:

53256

Middle Eastern (MID)

AF:

0.00574

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00963

AC:

10712

AN:

1111982

Other (OTH)

AF:

0.00679

AC:

410

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

700

1401

2101

2802

3502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.00704

AC:

1072

AN:

152330

Hom.:

Cov.:

AF XY:

0.00695

AC XY:

518

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

41590

American (AMR)

AF:

0.00601

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00104

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0120

AC:

127

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0103

AC:

700

AN:

68024

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

112

167

223

279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00924

Hom.:

Bravo

AF:

0.00623

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Sep 12, 2017

Athena Diagnostics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 04, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 15661075) -

Dec 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.82

CADD

Benign

0.57

(source)

DANN

Benign

0.61

PhyloP100

-0.16

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

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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