16-23185417-C-T

Variant names:

• chr16-23185417-C-T
• rs7404408
• NM_001039.4:c.-44-811C>T

Variant summary

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

The NM_001039.4(SCNN1G):​c.-44-811C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,068 control chromosomes in the GnomAD database, including 3,909 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 0.22 (3909 hom., cov: 32)
• Consequence: SCNN1G NM_001039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 6 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: Laboratory for Molecular Medicine, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• pseudohypoaldosteronism, type IB1, autosomal recessive

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

ENSG00000285613 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.305 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.-44-811C>T		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.-44-811C>T		intron	N/A	ENSP00000300061.2	P51170
	SCNN1G	ENST00000876141.1		c.-44-811C>T		intron	N/A	ENSP00000546200.1
	SCNN1G	ENST00000876140.1		c.-44-811C>T		intron	N/A	ENSP00000546199.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32953 AN: 151948 Hom.: 3889 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.217 AC: 33012 AN: 152068 Hom.: 3909 Cov.: 32 AF XY: 0.217 AC XY: 16135 AN XY: 74338

African (AFR) AF: 0.135 AC: 5615 AN: 41482

American (AMR) AF: 0.312 AC: 4766 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3468

East Asian (EAS) AF: 0.160 AC: 828 AN: 5178

South Asian (SAS) AF: 0.231 AC: 1114 AN: 4816

European-Finnish (FIN) AF: 0.242 AC: 2549 AN: 10548

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.242 AC: 16477 AN: 67990

Other (OTH) AF: 0.220 AC: 465 AN: 2110

Alfa AF: 0.226 Hom.: 770

Bravo AF: 0.221

Asia WGS AF: 0.216 AC: 749 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.087
DANN	Benign	0.28
PhyloP100		-2.5
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: rs7404408; hg19: chr16-23196738;