16-23348878-T-C

Position:

• chr16-23348878-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000336.3(SCNN1B):​c.279T>C​(p.Pro93Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,613,704 control chromosomes in the GnomAD database, including 294,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (36163 hom., cov: 30)
  • Exomes 𝑓: 0.58 (258772 hom.)
• Consequence: SCNN1B NM_000336.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: -3.32

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]

SCNN1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 16-23348878-T-C is Benign according to our data. Variant chr16-23348878-T-C is described in ClinVar as [Benign]. Clinvar id is 165167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23348878-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-3.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1B	NM_000336.3	c.279T>C	p.Pro93Pro	synonymous_variant	2/13	ENST00000343070.7	NP_000327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000343070.7	c.279T>C	p.Pro93Pro	synonymous_variant	2/13	1	NM_000336.3	ENSP00000345751.2

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101178 AN: 151872 Hom.: 36106 Cov.: 30

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.636

GnomAD3 exomes AF: 0.621 AC: 155174 AN: 249886 Hom.: 51891 AF XY: 0.629 AC XY: 84997 AN XY: 135178

Gnomad AFR exome AF: 0.914

Gnomad AMR exome AF: 0.435

Gnomad ASJ exome AF: 0.582

Gnomad EAS exome AF: 0.984

Gnomad SAS exome AF: 0.790

Gnomad FIN exome AF: 0.501

Gnomad NFE exome AF: 0.558

Gnomad OTH exome AF: 0.600

GnomAD4 exome AF: 0.584 AC: 853991 AN: 1461714 Hom.: 258772 Cov.: 60 AF XY: 0.590 AC XY: 428734 AN XY: 727148

Gnomad4 AFR exome AF: 0.918

Gnomad4 AMR exome AF: 0.441

Gnomad4 ASJ exome AF: 0.578

Gnomad4 EAS exome AF: 0.988

Gnomad4 SAS exome AF: 0.785

Gnomad4 FIN exome AF: 0.501

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.613

GnomAD4 genome AF: 0.666 AC: 101278 AN: 151990 Hom.: 36163 Cov.: 30 AF XY: 0.668 AC XY: 49640 AN XY: 74282

Gnomad4 AFR AF: 0.905

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.814

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.639

Alfa AF: 0.589 Hom.: 44328

Bravo AF: 0.674

Asia WGS AF: 0.896 AC: 3114 AN: 3478

EpiCase AF: 0.568

EpiControl AF: 0.581

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Pro93Pro in exon 2 of SCNN1B: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 45.2% (3883/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs238547). -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 24, 2017	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 21, 2014	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Pseudohypoaldosteronism, type IB1, autosomal recessive Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Liddle syndrome 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Bronchiectasis with or without elevated sweat chloride 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.28
DANN	Benign	0.58

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: rs238547; hg19: chr16-23360199;