16-23186733-C-T

Position:

• chr16-23186733-C-T

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.317+145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 730,490 control chromosomes in the GnomAD database, including 20,354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3651 hom., cov: 33)
  • Exomes 𝑓: 0.23 (16703 hom.)
• Consequence: SCNN1G NM_001039.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.950

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=-0.88).
• BP6: Variant 16-23186733-C-T is Benign according to our data. Variant chr16-23186733-C-T is described in ClinVar as [Benign]. Clinvar id is 1277809.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1G	NM_001039.4	c.317+145C>T		intron_variant		ENST00000300061.3	NP_001030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061.3	c.317+145C>T		intron_variant		1	NM_001039.4	ENSP00000300061	P1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31550 AN: 152018 Hom.: 3633 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.233 AC: 135043 AN: 578354 Hom.: 16703 AF XY: 0.233 AC XY: 72068 AN XY: 309158

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.208 AC: 31598 AN: 152136 Hom.: 3651 Cov.: 33 AF XY: 0.208 AC XY: 15497 AN XY: 74380

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.211

Alfa AF: 0.223 Hom.: 533

Bravo AF: 0.211

Asia WGS AF: 0.192 AC: 667 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	-0.88
CADD	Benign	1.2
DANN	Benign	0.65

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: rs12149898; hg19: chr16-23198054;