16-23209862-A-G

Position:

• chr16-23209862-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001039.4(SCNN1G):​c.1176+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,598,884 control chromosomes in the GnomAD database, including 514,858 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44833 hom., cov: 32)
  • Exomes 𝑓: 0.81 (470025 hom.)
• Consequence: SCNN1G NM_001039.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.0830

Genes affected

SCNN1G (HGNC:10602): (sodium channel epithelial 1 subunit gamma) 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 gamma subunit, and mutations in this gene have been associated with Liddle syndrome. [provided by RefSeq, Apr 2009]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-23209862-A-G is Benign according to our data. Variant chr16-23209862-A-G is described in ClinVar as [Benign]. Clinvar id is 165176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23209862-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCNN1G	NM_001039.4	c.1176+14A>G		intron_variant		ENST00000300061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCNN1G	ENST00000300061.3	c.1176+14A>G		intron_variant		1	NM_001039.4	P1
	ENST00000563471.1	n.101+3142T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115962 AN: 151938 Hom.: 44799 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.795

GnomAD3 exomes AF: 0.814 AC: 204052 AN: 250684 Hom.: 83653 AF XY: 0.815 AC XY: 110438 AN XY: 135484

Gnomad AFR exome AF: 0.647

Gnomad AMR exome AF: 0.898

Gnomad ASJ exome AF: 0.846

Gnomad EAS exome AF: 0.879

Gnomad SAS exome AF: 0.845

Gnomad FIN exome AF: 0.762

Gnomad NFE exome AF: 0.801

Gnomad OTH exome AF: 0.812

GnomAD4 exome AF: 0.805 AC: 1165060 AN: 1446828 Hom.: 470025 Cov.: 30 AF XY: 0.807 AC XY: 581610 AN XY: 720656

Gnomad4 AFR exome AF: 0.651

Gnomad4 AMR exome AF: 0.893

Gnomad4 ASJ exome AF: 0.850

Gnomad4 EAS exome AF: 0.894

Gnomad4 SAS exome AF: 0.847

Gnomad4 FIN exome AF: 0.756

Gnomad4 NFE exome AF: 0.801

Gnomad4 OTH exome AF: 0.802

GnomAD4 genome AF: 0.763 AC: 116048 AN: 152056 Hom.: 44833 Cov.: 32 AF XY: 0.763 AC XY: 56674 AN XY: 74298

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.831

Gnomad4 ASJ AF: 0.864

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.794

Alfa AF: 0.798 Hom.: 67886

Bravo AF: 0.767

Asia WGS AF: 0.779 AC: 2706 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	1176+14A>G in intron 7 of SCNN1G: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 34.5% (1518/4394) of African American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS; dbSNP rs5740). -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Liddle syndrome 2 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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Autosomal recessive pseudohypoaldosteronism type 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 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.26

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: rs5740; hg19: chr16-23221183;