16-23186241-A-G

Variant names:

• chr16-23186241-A-G
• rs5732
• NM_001039.4:c.-31A>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.-31A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,610,944 control chromosomes in the GnomAD database, including 44,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3589 hom., cov: 33)
  • Exomes 𝑓: 0.23 (41029 hom.)
• Consequence: SCNN1G NM_001039.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.38

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]

ENSG00000285613 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-23186241-A-G is Benign according to our data. Variant chr16-23186241-A-G is described in ClinVar as [Benign]. Clinvar id is 318344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23186241-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4	c.-31A>G		5_prime_UTR_variant	Exon 2 of 13	ENST00000300061.3	NP_001030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061	c.-31A>G		5_prime_UTR_variant	Exon 2 of 13	1	NM_001039.4	ENSP00000300061.2
ENSG00000285613	ENST00000648673.1	n.155T>C		non_coding_transcript_exon_variant	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31430 AN: 151950 Hom.: 3571 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.210

GnomAD3 exomes AF: 0.243 AC: 60641 AN: 249856 Hom.: 8009 AF XY: 0.238 AC XY: 32170 AN XY: 135280

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.395

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.152

Gnomad SAS exome AF: 0.230

Gnomad FIN exome AF: 0.246

Gnomad NFE exome AF: 0.232

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.233 AC: 339626 AN: 1458876 Hom.: 41029 Cov.: 32 AF XY: 0.233 AC XY: 169012 AN XY: 725894

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.207 AC: 31478 AN: 152068 Hom.: 3589 Cov.: 33 AF XY: 0.208 AC XY: 15453 AN XY: 74348

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.209

Alfa AF: 0.230 Hom.: 1125

Bravo AF: 0.211

Asia WGS AF: 0.193 AC: 668 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pseudohypoaldosteronism, type IB1, autosomal recessive Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Liddle syndrome 2 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.58

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: rs5732; hg19: chr16-23197562; COSMIC: COSV55599164;