rs13306653

Variant names:

• chr16-23213095-G-A
• rs13306653
• NM_001039.4:c.1432-7G>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.1432-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,610,694 control chromosomes in the GnomAD database, including 36,039 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3511 hom., cov: 31)
  • Exomes 𝑓: 0.20 (32528 hom.)
• Consequence: SCNN1G NM_001039.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002159
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: 0.720
• 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

ENSG00000260741 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-23213095-G-A is Benign according to our data. Variant chr16-23213095-G-A is described in ClinVar as Benign. ClinVar VariationId is 165175.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.1432-7G>A		splice_region intron	N/A	NP_001030.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1G	ENST00000300061.3	TSL:1 MANE Select	c.1432-7G>A		splice_region intron	N/A	ENSP00000300061.2
	SCNN1G	ENST00000876142.1		c.1432-7G>A		splice_region intron	N/A	ENSP00000546201.1
	SCNN1G	ENST00000876141.1		c.1408-7G>A		splice_region intron	N/A	ENSP00000546200.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32097 AN: 151716 Hom.: 3502 Cov.: 31

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.0614

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.208

GnomAD2 exomes AF: 0.175 AC: 44036 AN: 251434 AF XY: 0.172

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.0961

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.0626

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.215

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.205 AC: 298575 AN: 1458860 Hom.: 32528 Cov.: 33 AF XY: 0.201 AC XY: 146117 AN XY: 725874

African (AFR) AF: 0.251 AC: 8384 AN: 33408

American (AMR) AF: 0.105 AC: 4694 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 6090 AN: 26120

East Asian (EAS) AF: 0.0559 AC: 2218 AN: 39692

South Asian (SAS) AF: 0.0843 AC: 7271 AN: 86224

European-Finnish (FIN) AF: 0.223 AC: 11930 AN: 53418

Middle Eastern (MID) AF: 0.185 AC: 1064 AN: 5764

European-Non Finnish (NFE) AF: 0.220 AC: 244506 AN: 1109220

Other (OTH) AF: 0.206 AC: 12418 AN: 60296

GnomAD4 genome AF: 0.212 AC: 32135 AN: 151834 Hom.: 3511 Cov.: 31 AF XY: 0.208 AC XY: 15463 AN XY: 74212

African (AFR) AF: 0.246 AC: 10167 AN: 41348

American (AMR) AF: 0.162 AC: 2479 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 783 AN: 3466

East Asian (EAS) AF: 0.0612 AC: 316 AN: 5166

South Asian (SAS) AF: 0.0739 AC: 356 AN: 4818

European-Finnish (FIN) AF: 0.232 AC: 2446 AN: 10546

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.219 AC: 14905 AN: 67930

Other (OTH) AF: 0.215 AC: 451 AN: 2102

Alfa AF: 0.214 Hom.: 14877

Bravo AF: 0.207

Asia WGS AF: 0.110 AC: 382 AN: 3478

EpiCase AF: 0.215

EpiControl AF: 0.209

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	4	not specified (4)
-	-	2	Liddle syndrome 2 (2)
-	-	2	Pseudohypoaldosteronism, type IB1, autosomal recessive (2)
-	-	1	Bronchiectasis with or without elevated sweat chloride 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	13
DANN	Benign	0.61
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0040
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: rs13306653; hg19: chr16-23224416;