rs4499238

Variant names:

• chr16-23210058-T-C
• rs4499238
• NM_001039.4:c.1176+210T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-23210058-T-C
• chr16-23210058-T-A
• chr16-23210058-T-G

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.1176+210T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,182 control chromosomes in the GnomAD database, including 44,912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.76 (44912 hom., cov: 33)
• Consequence: SCNN1G NM_001039.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36
• Publications: 8 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-23210058-T-C is Benign according to our data. Variant chr16-23210058-T-C is described in ClinVar as Benign. ClinVar VariationId is 1282630.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 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+210T>C		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+210T>C		intron	N/A	ENSP00000300061.2	P51170
	SCNN1G	ENST00000876142.1		c.1176+210T>C		intron	N/A	ENSP00000546201.1
	SCNN1G	ENST00000876141.1		c.1176+210T>C		intron	N/A	ENSP00000546200.1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116103 AN: 152064 Hom.: 44878 Cov.: 33

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.763 AC: 116188 AN: 152182 Hom.: 44912 Cov.: 33 AF XY: 0.763 AC XY: 56776 AN XY: 74408

African (AFR) AF: 0.650 AC: 26971 AN: 41492

American (AMR) AF: 0.830 AC: 12686 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 2999 AN: 3470

East Asian (EAS) AF: 0.880 AC: 4558 AN: 5178

South Asian (SAS) AF: 0.846 AC: 4084 AN: 4826

European-Finnish (FIN) AF: 0.767 AC: 8135 AN: 10610

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

European-Non Finnish (NFE) AF: 0.795 AC: 54092 AN: 68010

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

Alfa AF: 0.761 Hom.: 9483

Bravo AF: 0.767

Asia WGS AF: 0.777 AC: 2700 AN: 3478

ClinVar

ClinVar submissions

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	-0.93
CADD	Benign	1.1
DANN	Benign	0.44
PhyloP100		-1.4
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: rs4499238; hg19: chr16-23221379;