16-23339348-A-C

Position:

• chr16-23339348-A-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCNN1B	NM_000336.3	c.-8-9244A>C		intron_variant		ENST00000343070.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCNN1B	ENST00000343070.7	c.-8-9244A>C		intron_variant		1	NM_000336.3	P1
SCNN1B	ENST00000307331.9	c.128-9244A>C		intron_variant		5
SCNN1B	ENST00000569789.1	n.179-9244A>C		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.0971

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0789

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0300

Gnomad4 NFE AF: 0.0953

Gnomad4 OTH AF: 0.127

Alfa AF: 0.100 Hom.: 1154

Bravo AF: 0.150

Asia WGS AF: 0.123 AC: 428 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.029
DANN	Benign	0.76

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: rs12447134; hg19: chr16-23350669;