16-23350509-T-G

Position:

• chr16-23350509-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1B	NM_000336.3	c.311+1599T>G		intron_variant		ENST00000343070.7	NP_000327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000343070.7	c.311+1599T>G		intron_variant		1	NM_000336.3	ENSP00000345751.2

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

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.0958

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.227

Alfa AF: 0.150 Hom.: 418

Bravo AF: 0.239

Asia WGS AF: 0.431 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.8
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs8044970; hg19: chr16-23361830;