Variant 16-23209862-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.0830

Variant links:

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]

SCNN1G links:

ENSG00000260741 (HGNC:):

ENSG00000260741 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4 link	c.1176+14A>G		intron_variant	Intron 7 of 12	ENST00000300061.3	NP_001030.2	P51170A5X2V1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061.3 link	c.1176+14A>G		intron_variant	Intron 7 of 12	1	NM_001039.4	ENSP00000300061.2		P51170
ENSG00000260741	ENST00000563471.1 link	n.101+3142T>C		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.763

AC:

115962

AN:

151938

Hom.:

44799

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.807

AC XY:

581610

AN XY:

720656

show subpopulations

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.:

AF XY:

0.763

AC XY:

56674

AN XY:

74298

show subpopulations

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:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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). -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Pseudohypoaldosteronism, type IB1, autosomal recessive

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Liddle syndrome 2

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bronchiectasis with or without elevated sweat chloride 3

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over