rs5728

Variant names:

• chr16-23216041-A-G
• rs5728
• NM_001039.4:c.*572A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4	c.*572A>G		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.*572A>G		3_prime_UTR_variant	Exon 13 of 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

African (AFR) AF: 0.328 AC: 88 AN: 268

American (AMR) AF: 0.416 AC: 1245 AN: 2990

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 109 AN: 258

East Asian (EAS) AF: 0.143 AC: 181 AN: 1262

South Asian (SAS) AF: 0.325 AC: 709 AN: 2184

European-Finnish (FIN) AF: 0.371 AC: 231 AN: 622

Middle Eastern (MID) AF: 0.313 AC: 20 AN: 64

European-Non Finnish (NFE) AF: 0.417 AC: 5488 AN: 13150

Other (OTH) AF: 0.418 AC: 464 AN: 1110

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

African (AFR) AF: 0.382 AC: 15840 AN: 41506

American (AMR) AF: 0.419 AC: 6409 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1479 AN: 3472

East Asian (EAS) AF: 0.184 AC: 951 AN: 5176

South Asian (SAS) AF: 0.332 AC: 1602 AN: 4826

European-Finnish (FIN) AF: 0.432 AC: 4563 AN: 10560

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30364 AN: 67988

Other (OTH) AF: 0.422 AC: 893 AN: 2114

Alfa AF: 0.434 Hom.: 39808

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 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	-0.95
CADD	Benign	4.8
DANN	Benign	0.76
PhyloP100		-0.045
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: rs5728; hg19: chr16-23227362;