rs5727

Variant names:

• chr16-23215737-G-A
• rs5727
• NM_001039.4:c.*268G>A

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.*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
• Publications: 8 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=-0.88).
• BP6: Variant 16-23215737-G-A is Benign according to our data. Variant chr16-23215737-G-A is described in ClinVar as Benign. ClinVar VariationId 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.

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.*268G>A		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.*268G>A		3_prime_UTR	Exon 13 of 13	ENSP00000300061.2	P51170
	SCNN1G	ENST00000876142.1		c.*268G>A		3_prime_UTR	Exon 12 of 12	ENSP00000546201.1
	SCNN1G	ENST00000876141.1		c.*268G>A		3_prime_UTR	Exon 13 of 13	ENSP00000546200.1

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

African (AFR) AF: 0.250 AC: 2782 AN: 11122

American (AMR) AF: 0.129 AC: 2151 AN: 16622

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 2786 AN: 11828

East Asian (EAS) AF: 0.0550 AC: 1384 AN: 25174

South Asian (SAS) AF: 0.0846 AC: 3769 AN: 44572

European-Finnish (FIN) AF: 0.227 AC: 5238 AN: 23068

Middle Eastern (MID) AF: 0.174 AC: 288 AN: 1652

European-Non Finnish (NFE) AF: 0.219 AC: 50813 AN: 231596

Other (OTH) AF: 0.204 AC: 4544 AN: 22306

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

African (AFR) AF: 0.246 AC: 10209 AN: 41502

American (AMR) AF: 0.163 AC: 2487 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 786 AN: 3470

East Asian (EAS) AF: 0.0612 AC: 317 AN: 5178

South Asian (SAS) AF: 0.0740 AC: 357 AN: 4824

European-Finnish (FIN) AF: 0.231 AC: 2444 AN: 10566

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14932 AN: 67982

Other (OTH) AF: 0.214 AC: 452 AN: 2114

Alfa AF: 0.221 Hom.: 782

Bravo AF: 0.207

Asia WGS AF: 0.110 AC: 382 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	-0.88
CADD	Benign	5.0
DANN	Benign	0.48
PhyloP100		0.15
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: rs5727; hg19: chr16-23227058;