chr16-23294425-T-C

Variant names:

• chr16-23294425-T-C
• rs2106374
• ENST00000569789.1:n.178+10621T>C

Variant summary

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

The ENST00000569789.1(SCNN1B):​n.178+10621T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,536 control chromosomes in the GnomAD database, including 2,530 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 0.18 (2530 hom., cov: 30)
• Consequence: SCNN1B ENST00000569789.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 1 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000569789.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1B	ENST00000569789.1	TSL:4	n.178+10621T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26714 AN: 151418 Hom.: 2523 Cov.: 30

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0903

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.176 AC: 26719 AN: 151536 Hom.: 2530 Cov.: 30 AF XY: 0.179 AC XY: 13259 AN XY: 74036

African (AFR) AF: 0.114 AC: 4696 AN: 41316

American (AMR) AF: 0.187 AC: 2840 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3462

East Asian (EAS) AF: 0.266 AC: 1352 AN: 5088

South Asian (SAS) AF: 0.246 AC: 1178 AN: 4794

European-Finnish (FIN) AF: 0.208 AC: 2181 AN: 10464

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13130 AN: 67898

Other (OTH) AF: 0.224 AC: 470 AN: 2098

Alfa AF: 0.193 Hom.: 7600

Bravo AF: 0.173

Asia WGS AF: 0.278 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.89
PhyloP100		0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2106374; hg19: chr16-23305746;