rs5728

Positions:

• chr16-23216041-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001039.4(SCNN1G):​c.*572A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 174,056 control chromosomes in the GnomAD database, including 14,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13204 hom., cov: 33)
  • Exomes 𝑓: 0.39 (1787 hom.)
• Consequence: SCNN1G NM_001039.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0450

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 16-23216041-A-G is Benign according to our data. Variant chr16-23216041-A-G is described in ClinVar as [Benign]. Clinvar id is 318367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1G	NM_001039.4	c.*572A>G		3_prime_UTR_variant	13/13	ENST00000300061.3	NP_001030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061.3	c.*572A>G		3_prime_UTR_variant	13/13	1	NM_001039.4	ENSP00000300061.2

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62613 AN: 152030 Hom.: 13174 Cov.: 33

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.390 AC: 8535 AN: 21908 Hom.: 1787 Cov.: 0 AF XY: 0.382 AC XY: 4263 AN XY: 11156

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.416

Gnomad4 ASJ exome AF: 0.422

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.371

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.418

GnomAD4 genome AF: 0.412 AC: 62700 AN: 152148 Hom.: 13204 Cov.: 33 AF XY: 0.406 AC XY: 30210 AN XY: 74374

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.422

Alfa AF: 0.438 Hom.: 24956

Bravo AF: 0.411

Asia WGS AF: 0.296 AC: 1028 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Pseudohypoaldosteronism, type IB1, autosomal recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Liddle syndrome 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.8
DANN	Benign	0.76

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

Other links and lift over

dbSNP: rs5728; hg19: chr16-23227362;