rs13306657

Variant names:

• chr16-23185981-C-T
• rs13306657
• NM_001039.4:c.-44-247C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001039.4(SCNN1G):​c.-44-247C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 151,964 control chromosomes in the GnomAD database, including 3,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3407 hom., cov: 33)
• Consequence: SCNN1G NM_001039.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0780
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-23185981-C-T is Benign according to our data. Variant chr16-23185981-C-T is described in ClinVar as Benign. ClinVar VariationId is 1283927.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.29 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.-44-247C>T		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.-44-247C>T		intron	N/A	ENSP00000300061.2	P51170
	SCNN1G	ENST00000876141.1		c.-44-247C>T		intron	N/A	ENSP00000546200.1
	SCNN1G	ENST00000876140.1		c.-44-247C>T		intron	N/A	ENSP00000546199.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29518 AN: 151844 Hom.: 3390 Cov.: 33

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.202

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.195 AC: 29561 AN: 151964 Hom.: 3407 Cov.: 33 AF XY: 0.196 AC XY: 14526 AN XY: 74300

African (AFR) AF: 0.0774 AC: 3197 AN: 41292

American (AMR) AF: 0.298 AC: 4553 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3472

East Asian (EAS) AF: 0.148 AC: 765 AN: 5164

South Asian (SAS) AF: 0.218 AC: 1050 AN: 4824

European-Finnish (FIN) AF: 0.240 AC: 2542 AN: 10604

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15845 AN: 67998

Other (OTH) AF: 0.201 AC: 425 AN: 2112

Alfa AF: 0.211 Hom.: 518

Bravo AF: 0.196

Asia WGS AF: 0.181 AC: 628 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.4
DANN	Benign	0.90
PhyloP100		-0.078
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: rs13306657; hg19: chr16-23197302;