16-23189132-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001039.4(SCNN1G):c.318-239T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 152,182 control chromosomes in the GnomAD database, including 345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.059 (345 hom., cov: 32)
• Consequence: SCNN1G NM_001039.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.196

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-23189132-T-A is Benign according to our data. Variant chr16-23189132-T-A is described in ClinVar as [Benign]. Clinvar id is 1236992.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCNN1G	NM_001039.4	c.318-239T>A		intron_variant		ENST00000300061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCNN1G	ENST00000300061.3	c.318-239T>A		intron_variant		1	NM_001039.4	P1

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 8921 AN: 152062 Hom.: 340 Cov.: 32

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0491

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.0382

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0739

Gnomad OTH AF: 0.0580

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

GnomAD4 genome AF: 0.0588 AC: 8943 AN: 152182 Hom.: 345 Cov.: 32 AF XY: 0.0605 AC XY: 4498 AN XY: 74372

Gnomad4 AFR AF: 0.0299

Gnomad4 AMR AF: 0.0489

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.0186

Gnomad4 SAS AF: 0.0378

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0739

Gnomad4 OTH AF: 0.0583

Alfa AF: 0.0738 Hom.: 60

Bravo AF: 0.0517

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 04, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.7
Dann	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs72646493; hg19: chr16-23200453;