NM_000336.3:c.1466+113G>C

Variant names:

• chr16-23378880-G-C
• rs2303153
• NM_000336.3:c.1466+113G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000336.3(SCNN1B):​c.1466+113G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 988,058 control chromosomes in the GnomAD database, including 159,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (29223 hom., cov: 30)
  • Exomes 𝑓: 0.55 (130554 hom.)
• Consequence: SCNN1B NM_000336.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0720
• Publications: 9 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 16-23378880-G-C is Benign according to our data. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23378880-G-C is described in CliVar as Benign. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1B	NM_000336.3	c.1466+113G>C		intron_variant	Intron 11 of 12	ENST00000343070.7	NP_000327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000343070.7	c.1466+113G>C		intron_variant	Intron 11 of 12	1	NM_000336.3	ENSP00000345751.2

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91477 AN: 151786 Hom.: 29163 Cov.: 30

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.587

GnomAD4 exome AF: 0.547 AC: 457034 AN: 836154 Hom.: 130554 AF XY: 0.549 AC XY: 238154 AN XY: 434128

African (AFR) AF: 0.770 AC: 16451 AN: 21364

American (AMR) AF: 0.736 AC: 27078 AN: 36776

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 9198 AN: 20916

East Asian (EAS) AF: 0.883 AC: 31002 AN: 35092

South Asian (SAS) AF: 0.686 AC: 47315 AN: 68996

European-Finnish (FIN) AF: 0.473 AC: 22514 AN: 47568

Middle Eastern (MID) AF: 0.500 AC: 1862 AN: 3722

European-Non Finnish (NFE) AF: 0.497 AC: 279527 AN: 562126

Other (OTH) AF: 0.558 AC: 22087 AN: 39594

GnomAD4 genome AF: 0.603 AC: 91604 AN: 151904 Hom.: 29223 Cov.: 30 AF XY: 0.606 AC XY: 44998 AN XY: 74244

African (AFR) AF: 0.773 AC: 32024 AN: 41420

American (AMR) AF: 0.661 AC: 10084 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1538 AN: 3468

East Asian (EAS) AF: 0.864 AC: 4461 AN: 5164

South Asian (SAS) AF: 0.700 AC: 3369 AN: 4814

European-Finnish (FIN) AF: 0.461 AC: 4870 AN: 10554

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33464 AN: 67906

Other (OTH) AF: 0.592 AC: 1252 AN: 2114

Alfa AF: 0.371 Hom.: 849

Bravo AF: 0.625

Asia WGS AF: 0.762 AC: 2649 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

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	-1.0
CADD	Benign	5.8
DANN	Benign	0.48
PhyloP100		-0.072
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2303153; hg19: chr16-23390201; COSMIC: COSV56308340;