rs152745

Variant names:

• chr16-23355101-G-A
• rs152745
• NM_000336.3:c.586-198G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-23355101-G-A
• chr16-23355101-G-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.586-198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,954 control chromosomes in the GnomAD database, including 25,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (25819 hom., cov: 32)
• Consequence: SCNN1B NM_000336.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01
• Publications: 15 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=-0.91).
• BP6: Variant 16-23355101-G-A is Benign according to our data. Variant chr16-23355101-G-A is described in ClinVar as Benign. ClinVar VariationId is 1250858.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1B	NM_000336.3	c.586-198G>A		intron_variant	Intron 3 of 12	ENST00000343070.7	NP_000327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000343070.7	c.586-198G>A		intron_variant	Intron 3 of 12	1	NM_000336.3	ENSP00000345751.2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82303 AN: 151836 Hom.: 25768 Cov.: 32

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.488

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.542 AC: 82400 AN: 151954 Hom.: 25819 Cov.: 32 AF XY: 0.544 AC XY: 40386 AN XY: 74260

African (AFR) AF: 0.863 AC: 35769 AN: 41462

American (AMR) AF: 0.405 AC: 6193 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1395 AN: 3470

East Asian (EAS) AF: 0.800 AC: 4118 AN: 5148

South Asian (SAS) AF: 0.609 AC: 2929 AN: 4810

European-Finnish (FIN) AF: 0.388 AC: 4095 AN: 10564

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26231 AN: 67908

Other (OTH) AF: 0.489 AC: 1031 AN: 2108

Alfa AF: 0.437 Hom.: 70467

Bravo AF: 0.557

Asia WGS AF: 0.683 AC: 2374 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	-0.91
CADD	Benign	0.35
DANN	Benign	0.43
PhyloP100		-1.0
PromoterAI		0.041	Neutral
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: rs152745; hg19: chr16-23366422;