rs5727

Positions:

• chr16-23215737-G-A

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.*268G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 540,078 control chromosomes in the GnomAD database, including 11,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3524 hom., cov: 32)
  • Exomes 𝑓: 0.19 (7835 hom.)
• Consequence: SCNN1G NM_001039.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.149

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=-0.88).
• BP6: Variant 16-23215737-G-A is Benign according to our data. Variant chr16-23215737-G-A is described in ClinVar as [Benign]. Clinvar id is 318365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1G	NM_001039.4	c.*268G>A		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.*268G>A		3_prime_UTR_variant	13/13	1	NM_001039.4	ENSP00000300061.2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32179 AN: 152020 Hom.: 3515 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0615

Gnomad SAS AF: 0.0739

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.190 AC: 73755 AN: 387940 Hom.: 7835 Cov.: 3 AF XY: 0.183 AC XY: 37701 AN XY: 205770

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.0550

Gnomad4 SAS exome AF: 0.0846

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.212 AC: 32217 AN: 152138 Hom.: 3524 Cov.: 32 AF XY: 0.208 AC XY: 15489 AN XY: 74368

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0612

Gnomad4 SAS AF: 0.0740

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.214

Alfa AF: 0.220 Hom.: 766

Bravo AF: 0.207

Asia WGS AF: 0.110 AC: 382 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 22, 2019	- -

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	-0.88
CADD	Benign	5.0
DANN	Benign	0.48

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: rs5727; hg19: chr16-23227058;