16-23339348-A-C

Variant names:

• chr16-23339348-A-C
• rs12447134
• NM_000336.3:c.-8-9244A>C

Variant summary

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

The NM_000336.3(SCNN1B):​c.-8-9244A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 151,920 control chromosomes in the GnomAD database, including 2,026 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 0.14 (2026 hom., cov: 31)
• Consequence: SCNN1B NM_000336.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 8 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, 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1B	NM_000336.3	MANE Select	c.-8-9244A>C		intron	N/A	NP_000327.2	B2R812
	SCNN1B	NM_001410900.1		c.-8-9244A>C		intron	N/A	NP_001397829.1	H3BQ95

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1B	ENST00000343070.7	TSL:1 MANE Select	c.-8-9244A>C		intron	N/A	ENSP00000345751.2	P51168-1
	SCNN1B	ENST00000307331.9	TSL:5	c.128-9244A>C		intron	N/A	ENSP00000302874.5	P51168-2
	SCNN1B	ENST00000962247.1		c.-8-9244A>C		intron	N/A	ENSP00000632306.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21309 AN: 151804 Hom.: 2017 Cov.: 31

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0952

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.141 AC: 21359 AN: 151920 Hom.: 2026 Cov.: 31 AF XY: 0.136 AC XY: 10086 AN XY: 74282

African (AFR) AF: 0.270 AC: 11178 AN: 41366

American (AMR) AF: 0.0971 AC: 1481 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3470

East Asian (EAS) AF: 0.0789 AC: 408 AN: 5174

South Asian (SAS) AF: 0.128 AC: 613 AN: 4792

European-Finnish (FIN) AF: 0.0300 AC: 317 AN: 10582

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0953 AC: 6474 AN: 67966

Other (OTH) AF: 0.127 AC: 268 AN: 2116

Alfa AF: 0.107 Hom.: 1732

Bravo AF: 0.150

Asia WGS AF: 0.123 AC: 428 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.029
DANN	Benign	0.76
PhyloP100		-1.7
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: rs12447134; hg19: chr16-23350669;