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
• Liddle syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Laboratory for Molecular Medicine, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• pseudohypoaldosteronism, type IB1, autosomal recessive

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1G	NM_001039.4	MANE Select	c.*572A>G		3_prime_UTR	Exon 13 of 13	NP_001030.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1G	ENST00000300061.3	TSL:1 MANE Select	c.*572A>G		3_prime_UTR	Exon 13 of 13	ENSP00000300061.2	P51170
	SCNN1G	ENST00000876142.1		c.*572A>G		3_prime_UTR	Exon 12 of 12	ENSP00000546201.1
	SCNN1G	ENST00000876141.1		c.*572A>G		3_prime_UTR	Exon 13 of 13	ENSP00000546200.1

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Liddle syndrome 2 (1)
-	-	1	Pseudohypoaldosteronism, type IB1, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

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;