rs4073291

Variant names:

• chr16-23184672-A-C
• rs4073291
• NM_001039.4:c.-44-1556A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001039.4(SCNN1G):​c.-44-1556A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 151,872 control chromosomes in the GnomAD database, including 3,630 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3630 hom., cov: 31)
• Consequence: SCNN1G NM_001039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 9 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
• Liddle syndrome 2

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

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

ENSG00000285613 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1G	NM_001039.4	MANE Select	c.-44-1556A>C		intron	N/A	NP_001030.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1G	ENST00000300061.3	TSL:1 MANE Select	c.-44-1556A>C		intron	N/A	ENSP00000300061.2	P51170
	SCNN1G	ENST00000876141.1		c.-44-1556A>C		intron	N/A	ENSP00000546200.1
	SCNN1G	ENST00000876140.1		c.-44-1556A>C		intron	N/A	ENSP00000546199.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31436 AN: 151754 Hom.: 3612 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.207 AC: 31485 AN: 151872 Hom.: 3630 Cov.: 31 AF XY: 0.208 AC XY: 15438 AN XY: 74206

African (AFR) AF: 0.118 AC: 4873 AN: 41426

American (AMR) AF: 0.307 AC: 4687 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 850 AN: 3460

East Asian (EAS) AF: 0.159 AC: 819 AN: 5160

South Asian (SAS) AF: 0.222 AC: 1065 AN: 4802

European-Finnish (FIN) AF: 0.239 AC: 2513 AN: 10514

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15901 AN: 67940

Other (OTH) AF: 0.210 AC: 441 AN: 2104

Alfa AF: 0.229 Hom.: 794

Bravo AF: 0.211

Asia WGS AF: 0.193 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.74
PhyloP100		-0.050
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4073291;

hg19: chr16-23195993;