16-23350509-T-G

Variant names:

• chr16-23350509-T-G
• rs8044970
• NM_000336.3:c.311+1599T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000336.3(SCNN1B):​c.311+1599T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,062 control chromosomes in the GnomAD database, including 4,725 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4725 hom., cov: 32)
• Consequence: SCNN1B NM_000336.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.477 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1B	NM_000336.3	MANE Select	c.311+1599T>G		intron	N/A	NP_000327.2
	SCNN1B	NM_001410900.1		c.311+1599T>G		intron	N/A	NP_001397829.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1B	ENST00000343070.7	TSL:1 MANE Select	c.311+1599T>G		intron	N/A	ENSP00000345751.2
	SCNN1B	ENST00000307331.9	TSL:5	c.446+1599T>G		intron	N/A	ENSP00000302874.5
	SCNN1B	ENST00000568923.5	TSL:3	c.311+1599T>G		intron	N/A	ENSP00000456309.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35599 AN: 151944 Hom.: 4713 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.0958

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.234 AC: 35648 AN: 152062 Hom.: 4725 Cov.: 32 AF XY: 0.235 AC XY: 17497 AN XY: 74320

African (AFR) AF: 0.315 AC: 13064 AN: 41474

American (AMR) AF: 0.190 AC: 2897 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 610 AN: 3470

East Asian (EAS) AF: 0.412 AC: 2129 AN: 5168

South Asian (SAS) AF: 0.493 AC: 2376 AN: 4818

European-Finnish (FIN) AF: 0.0958 AC: 1011 AN: 10554

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12747 AN: 67978

Other (OTH) AF: 0.227 AC: 480 AN: 2116

Alfa AF: 0.156 Hom.: 463

Bravo AF: 0.239

Asia WGS AF: 0.431 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.8
DANN	Benign	0.44
PhyloP100		0.80
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: rs8044970; hg19: chr16-23361830;