rs239345

Positions:

• chr16-23334617-T-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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/exons	MANE	Protein	UniProt
SCNN1B	NM_000336.3	c.-8-13975T>A		intron_variant		ENST00000343070.7	NP_000327.2
SCNN1B	NM_001410900.1	c.-8-13975T>A		intron_variant			NP_001397829.1
SCNN1B	XM_011545913.3	c.25+11039T>A		intron_variant			XP_011544215.1
SCNN1B	XM_017023525.2	c.50-13975T>A		intron_variant			XP_016879014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000343070.7	c.-8-13975T>A		intron_variant		1	NM_000336.3	ENSP00000345751	P1
SCNN1B	ENST00000307331.9	c.127+11039T>A		intron_variant		5		ENSP00000302874
SCNN1B	ENST00000569789.1	n.179-13975T>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.303

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

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: rs239345; hg19: chr16-23345938;