rs5740

Variant names:

• chr16-23209862-A-G
• rs5740
• NM_001039.4:c.1176+14A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-23209862-A-G
• chr16-23209862-A-C
• chr16-23209862-A-T

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.1176+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,598,884 control chromosomes in the GnomAD database, including 514,858 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44833 hom., cov: 32)
  • Exomes 𝑓: 0.81 (470025 hom.)
• Consequence: SCNN1G NM_001039.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.0830
• Publications: 20 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

ENSG00000260741 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-23209862-A-G is Benign according to our data. Variant chr16-23209862-A-G is described in ClinVar as Benign. ClinVar VariationId is 165176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 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.1176+14A>G		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.1176+14A>G		intron	N/A	ENSP00000300061.2	P51170
	SCNN1G	ENST00000876142.1		c.1176+14A>G		intron	N/A	ENSP00000546201.1
	SCNN1G	ENST00000876141.1		c.1176+14A>G		intron	N/A	ENSP00000546200.1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115962 AN: 151938 Hom.: 44799 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.795

GnomAD2 exomes AF: 0.814 AC: 204052 AN: 250684 AF XY: 0.815

Gnomad AFR exome AF: 0.647

Gnomad AMR exome AF: 0.898

Gnomad ASJ exome AF: 0.846

Gnomad EAS exome AF: 0.879

Gnomad FIN exome AF: 0.762

Gnomad NFE exome AF: 0.801

Gnomad OTH exome AF: 0.812

GnomAD4 exome AF: 0.805 AC: 1165060 AN: 1446828 Hom.: 470025 Cov.: 30 AF XY: 0.807 AC XY: 581610 AN XY: 720656

African (AFR) AF: 0.651 AC: 21551 AN: 33112

American (AMR) AF: 0.893 AC: 39914 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 22167 AN: 26068

East Asian (EAS) AF: 0.894 AC: 35414 AN: 39624

South Asian (SAS) AF: 0.847 AC: 72796 AN: 85952

European-Finnish (FIN) AF: 0.756 AC: 40354 AN: 53390

Middle Eastern (MID) AF: 0.832 AC: 4780 AN: 5748

European-Non Finnish (NFE) AF: 0.801 AC: 880031 AN: 1098298

Other (OTH) AF: 0.802 AC: 48053 AN: 59934

GnomAD4 genome AF: 0.763 AC: 116048 AN: 152056 Hom.: 44833 Cov.: 32 AF XY: 0.763 AC XY: 56674 AN XY: 74298

African (AFR) AF: 0.649 AC: 26902 AN: 41448

American (AMR) AF: 0.831 AC: 12712 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 3000 AN: 3472

East Asian (EAS) AF: 0.879 AC: 4528 AN: 5152

South Asian (SAS) AF: 0.847 AC: 4081 AN: 4818

European-Finnish (FIN) AF: 0.767 AC: 8095 AN: 10558

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.795 AC: 54067 AN: 67994

Other (OTH) AF: 0.794 AC: 1676 AN: 2112

Alfa AF: 0.791 Hom.: 166832

Bravo AF: 0.767

Asia WGS AF: 0.779 AC: 2706 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	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	-0.88
CADD	Benign	1.1
DANN	Benign	0.26
PhyloP100		-0.083
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: rs5740; hg19: chr16-23221183;