rs5732

Variant names:

• chr16-23186241-A-G
• rs5732
• NM_001039.4:c.-31A>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.-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
• Publications: 14 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• pseudohypoaldosteronism, type IB1, autosomal recessive

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000285613 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 318344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.299 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.-31A>G		5_prime_UTR	Exon 2 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.-31A>G		5_prime_UTR	Exon 2 of 13	ENSP00000300061.2	P51170
	SCNN1G	ENST00000876142.1		c.-31A>G		5_prime_UTR	Exon 1 of 12	ENSP00000546201.1
	SCNN1G	ENST00000876141.1		c.-31A>G		5_prime_UTR	Exon 2 of 13	ENSP00000546200.1

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

GnomAD2 exomes AF: 0.243 AC: 60641 AN: 249856 AF XY: 0.238

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 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

African (AFR) AF: 0.113 AC: 3786 AN: 33430

American (AMR) AF: 0.391 AC: 17415 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 6512 AN: 26116

East Asian (EAS) AF: 0.145 AC: 5770 AN: 39678

South Asian (SAS) AF: 0.231 AC: 19882 AN: 86102

European-Finnish (FIN) AF: 0.244 AC: 13005 AN: 53394

Middle Eastern (MID) AF: 0.198 AC: 1140 AN: 5766

European-Non Finnish (NFE) AF: 0.233 AC: 258181 AN: 1109508

Other (OTH) AF: 0.231 AC: 13935 AN: 60298

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

African (AFR) AF: 0.118 AC: 4881 AN: 41532

American (AMR) AF: 0.307 AC: 4688 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 852 AN: 3464

East Asian (EAS) AF: 0.159 AC: 821 AN: 5176

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4814

European-Finnish (FIN) AF: 0.238 AC: 2516 AN: 10564

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15879 AN: 67932

Other (OTH) AF: 0.209 AC: 440 AN: 2106

Alfa AF: 0.230 Hom.: 1725

Bravo AF: 0.211

Asia WGS AF: 0.193 AC: 668 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.80
CADD	Benign	4.0
DANN	Benign	0.58
PhyloP100		-1.4
Mutation Taster		=300/0	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: rs5732; hg19: chr16-23197562; COSMIC: COSV55599164;