16-23184325-T-C

Variant names:

• chr16-23184325-T-C
• rs4073930
• NM_001039.4:c.-45+1512T>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.-45+1512T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,018 control chromosomes in the GnomAD database, including 3,638 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 (3638 hom., cov: 32)
• Consequence: SCNN1G NM_001039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417
• Publications: 14 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

ENSG00000285613 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4	c.-45+1512T>C		intron_variant	Intron 1 of 12	ENST00000300061.3	NP_001030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061.3	c.-45+1512T>C		intron_variant	Intron 1 of 12	1	NM_001039.4	ENSP00000300061.2
ENSG00000285613	ENST00000648673.1	n.193+1878A>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31497 AN: 151900 Hom.: 3620 Cov.: 32

Gnomad AFR AF: 0.118

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: 0.244

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.208 AC: 31545 AN: 152018 Hom.: 3638 Cov.: 32 AF XY: 0.208 AC XY: 15492 AN XY: 74332

African (AFR) AF: 0.118 AC: 4890 AN: 41476

American (AMR) AF: 0.307 AC: 4690 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 854 AN: 3468

East Asian (EAS) AF: 0.159 AC: 822 AN: 5156

South Asian (SAS) AF: 0.222 AC: 1065 AN: 4804

European-Finnish (FIN) AF: 0.239 AC: 2530 AN: 10568

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15912 AN: 67956

Other (OTH) AF: 0.211 AC: 445 AN: 2112

Alfa AF: 0.228 Hom.: 15787

Bravo AF: 0.211

Asia WGS AF: 0.192 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.2
DANN	Benign	0.74
PhyloP100		0.42
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: rs4073930; hg19: chr16-23195646;