rs239345

Variant names:

• chr16-23334617-T-A
• rs239345
• NM_000336.3:c.-8-13975T>A

Variant summary

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

The NM_000336.3(SCNN1B):​c.-8-13975T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,102 control chromosomes in the GnomAD database, including 6,003 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 0.28 (6003 hom., cov: 32)
• Consequence: SCNN1B NM_000336.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1B	NM_000336.3	c.-8-13975T>A		intron_variant	Intron 1 of 12	ENST00000343070.7	NP_000327.2
SCNN1B	NM_001410900.1	c.-8-13975T>A		intron_variant	Intron 1 of 11		NP_001397829.1
SCNN1B	XM_017023525.2	c.50-13975T>A		intron_variant	Intron 2 of 13		XP_016879014.1
SCNN1B	XM_011545913.3	c.25+11039T>A		intron_variant	Intron 2 of 13		XP_011544215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000343070.7	c.-8-13975T>A		intron_variant	Intron 1 of 12	1	NM_000336.3	ENSP00000345751.2
SCNN1B	ENST00000307331.9	c.127+11039T>A		intron_variant	Intron 2 of 13	5		ENSP00000302874.5
SCNN1B	ENST00000569789.1	n.179-13975T>A		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41816 AN: 151984 Hom.: 5993 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.275 AC: 41847 AN: 152102 Hom.: 6003 Cov.: 32 AF XY: 0.274 AC XY: 20341 AN XY: 74364

African (AFR) AF: 0.358 AC: 14859 AN: 41474

American (AMR) AF: 0.231 AC: 3524 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3472

East Asian (EAS) AF: 0.215 AC: 1109 AN: 5168

South Asian (SAS) AF: 0.240 AC: 1155 AN: 4822

European-Finnish (FIN) AF: 0.236 AC: 2494 AN: 10582

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17109 AN: 67988

Other (OTH) AF: 0.303 AC: 639 AN: 2112

Alfa AF: 0.271 Hom.: 691

Bravo AF: 0.281

Asia WGS AF: 0.265 AC: 920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.018
DANN	Benign	0.47
PhyloP100		-1.9
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: rs239345; hg19: chr16-23345938;