16-23189272-T-C

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.318-99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,246,104 control chromosomes in the GnomAD database, including 58,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6193 hom., cov: 32)
  • Exomes 𝑓: 0.31 (52595 hom.)
• Consequence: SCNN1G NM_001039.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.853

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=-0.89).
• BP6: Variant 16-23189272-T-C is Benign according to our data. Variant chr16-23189272-T-C is described in ClinVar as [Benign]. Clinvar id is 1266779.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCNN1G	NM_001039.4	c.318-99T>C		intron_variant		ENST00000300061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCNN1G	ENST00000300061.3	c.318-99T>C		intron_variant		1	NM_001039.4	P1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41422 AN: 152002 Hom.: 6170 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.305 AC: 333718 AN: 1093982 Hom.: 52595 AF XY: 0.304 AC XY: 170304 AN XY: 560540

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.430

Gnomad4 ASJ exome AF: 0.307

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.364

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.273 AC: 41496 AN: 152122 Hom.: 6193 Cov.: 32 AF XY: 0.275 AC XY: 20411 AN XY: 74342

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.275

Alfa AF: 0.304 Hom.: 968

Bravo AF: 0.269

Asia WGS AF: 0.274 AC: 950 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.57
Dann	Benign	0.61

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: rs11865345; hg19: chr16-23200593;