chr16-23185983-CACGGCTAGG-C

Variant names:

• chr16-23185983-CACGGCTAGG-C
• rs201153561
• NM_001039.4:c.-44-244_-44-236delACGGCTAGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001039.4(SCNN1G):​c.-44-244_-44-236delACGGCTAGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 152,322 control chromosomes in the GnomAD database, including 27 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.011 (27 hom., cov: 32)
• Consequence: SCNN1G NM_001039.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16
• Publications: 0 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

ENSG00000285613 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 16-23185983-CACGGCTAGG-C is Benign according to our data. Variant chr16-23185983-CACGGCTAGG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1699900.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.011 (1675/152322) while in subpopulation AFR AF = 0.0351 (1458/41558). AF 95% confidence interval is 0.0336. There are 27 homozygotes in GnomAd4. There are 805 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AD,AR gene

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.-44-244_-44-236delACGGCTAGG		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.-44-244_-44-236delACGGCTAGG		intron	N/A	ENSP00000300061.2	P51170
	SCNN1G	ENST00000876141.1		c.-44-244_-44-236delACGGCTAGG		intron	N/A	ENSP00000546200.1
	SCNN1G	ENST00000876140.1		c.-44-244_-44-236delACGGCTAGG		intron	N/A	ENSP00000546199.1

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1670 AN: 152204 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0351

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.00621

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

GnomAD4 genome AF: 0.0110 AC: 1675 AN: 152322 Hom.: 27 Cov.: 32 AF XY: 0.0108 AC XY: 805 AN XY: 74492

African (AFR) AF: 0.0351 AC: 1458 AN: 41558

American (AMR) AF: 0.00529 AC: 81 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5184

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000823 AC: 56 AN: 68026

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.000224 Hom.: 0

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201153561; hg19: chr16-23197304;