rs5729

Variant names:

• chr16-23216075-T-A
• rs5729
• NM_001039.4:c.*606T>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.*606T>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 0.206 in 161,576 control chromosomes in the GnomAD database, including 3,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3528 hom., cov: 33)
  • Exomes 𝑓: 0.12 (82 hom.)
• Consequence: SCNN1G NM_001039.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.388

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=-0.89).
• BP6: Variant 16-23216075-T-A is Benign according to our data. Variant chr16-23216075-T-A is described in ClinVar as [Benign]. Clinvar id is 318370.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 rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4	c.*606T>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000300061.3	NP_001030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061.3	c.*606T>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_001039.4	ENSP00000300061.2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32186 AN: 152046 Hom.: 3519 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.117 AC: 1102 AN: 9412 Hom.: 82 Cov.: 0 AF XY: 0.112 AC XY: 531 AN XY: 4744

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.0864

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.0128

Gnomad4 SAS exome AF: 0.0336

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.212 AC: 32224 AN: 152164 Hom.: 3528 Cov.: 33 AF XY: 0.208 AC XY: 15504 AN XY: 74400

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0611

Gnomad4 SAS AF: 0.0742

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.216

Alfa AF: 0.226 Hom.: 511

Bravo AF: 0.207

Asia WGS AF: 0.110 AC: 381 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

- -

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pseudohypoaldosteronism, type IB1, autosomal recessive Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.89
CADD	Benign	1.1
DANN	Benign	0.60

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: rs5729; hg19: chr16-23227396;