16-23209917-A-G

Variant names:

• chr16-23209917-A-G
• rs4281710
• NM_001039.4:c.1176+69A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001039.4(SCNN1G):​c.1176+69A>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 1,108,250 control chromosomes in the GnomAD database, including 357,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44855 hom., cov: 32)
  • Exomes 𝑓: 0.81 (313017 hom.)
• Consequence: SCNN1G NM_001039.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.285
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• Liddle syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• bronchiectasis with or without elevated sweat chloride 3

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• Liddle syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• pseudohypoaldosteronism, type IB1, autosomal recessive

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000260741 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-23209917-A-G is Benign according to our data. Variant chr16-23209917-A-G is described in ClinVar as Benign. ClinVar VariationId is 1289716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4	c.1176+69A>G		intron_variant	Intron 7 of 12	ENST00000300061.3	NP_001030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061.3	c.1176+69A>G		intron_variant	Intron 7 of 12	1	NM_001039.4	ENSP00000300061.2
ENSG00000260741	ENST00000563471.1	n.101+3087T>C		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.763 AC: 116016 AN: 152032 Hom.: 44821 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.795

GnomAD4 exome AF: 0.808 AC: 772122 AN: 956098 Hom.: 313017 AF XY: 0.809 AC XY: 401068 AN XY: 495654

African (AFR) AF: 0.651 AC: 15485 AN: 23784

American (AMR) AF: 0.892 AC: 37282 AN: 41794

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 19385 AN: 22766

East Asian (EAS) AF: 0.892 AC: 33013 AN: 37016

South Asian (SAS) AF: 0.847 AC: 63717 AN: 75196

European-Finnish (FIN) AF: 0.756 AC: 39211 AN: 51878

Middle Eastern (MID) AF: 0.837 AC: 4012 AN: 4794

European-Non Finnish (NFE) AF: 0.801 AC: 524961 AN: 655118

Other (OTH) AF: 0.801 AC: 35056 AN: 43752

GnomAD4 genome AF: 0.763 AC: 116104 AN: 152152 Hom.: 44855 Cov.: 32 AF XY: 0.763 AC XY: 56723 AN XY: 74388

African (AFR) AF: 0.649 AC: 26912 AN: 41478

American (AMR) AF: 0.831 AC: 12715 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 3000 AN: 3472

East Asian (EAS) AF: 0.879 AC: 4549 AN: 5178

South Asian (SAS) AF: 0.847 AC: 4085 AN: 4824

European-Finnish (FIN) AF: 0.767 AC: 8113 AN: 10576

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.795 AC: 54067 AN: 68010

Other (OTH) AF: 0.794 AC: 1678 AN: 2114

Alfa AF: 0.792 Hom.: 61063

Bravo AF: 0.767

Asia WGS AF: 0.777 AC: 2700 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4281710; hg19: chr16-23221238;