rs152740

Positions:

• chr16-23357769-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000336.3(SCNN1B):​c.776+2280A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,982 control chromosomes in the GnomAD database, including 16,654 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 0.45 (16654 hom., cov: 32)
• Consequence: SCNN1B NM_000336.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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 (EAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1B	NM_000336.3	c.776+2280A>T		intron_variant		ENST00000343070.7	NP_000327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000343070.7	c.776+2280A>T		intron_variant		1	NM_000336.3	ENSP00000345751	P1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67960 AN: 151864 Hom.: 16634 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.447 AC: 68010 AN: 151982 Hom.: 16654 Cov.: 32 AF XY: 0.451 AC XY: 33502 AN XY: 74256

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.419

Alfa AF: 0.398 Hom.: 1597

Bravo AF: 0.455

Asia WGS AF: 0.653 AC: 2271 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	0.22
DANN	Benign	0.69

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: rs152740; hg19: chr16-23369090;