rs152745

Positions:

• chr16-23355101-G-A
• chr16-23355101-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000336.3(SCNN1B):​c.586-198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,954 control chromosomes in the GnomAD database, including 25,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (25819 hom., cov: 32)
• Consequence: SCNN1B NM_000336.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-23355101-G-A is Benign according to our data. Variant chr16-23355101-G-A is described in ClinVar as [Benign]. Clinvar id is 1250858.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1B	NM_000336.3	c.586-198G>A		intron_variant		ENST00000343070.7	NP_000327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000343070.7	c.586-198G>A		intron_variant		1	NM_000336.3	ENSP00000345751.2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82303 AN: 151836 Hom.: 25768 Cov.: 32

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.542 AC: 82400 AN: 151954 Hom.: 25819 Cov.: 32 AF XY: 0.544 AC XY: 40386 AN XY: 74260

Gnomad4 AFR AF: 0.863

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.489

Alfa AF: 0.413 Hom.: 27917

Bravo AF: 0.557

Asia WGS AF: 0.683 AC: 2374 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.43

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: rs152745; hg19: chr16-23366422;