16-23186868-G-A

Variant names:

• chr16-23186868-G-A
• rs9797088
• NM_001039.4:c.317+280G>A

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.317+280G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 151,952 control chromosomes in the GnomAD database, including 3,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3624 hom., cov: 32)
• Consequence: SCNN1G NM_001039.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.816

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 16-23186868-G-A is Benign according to our data. Variant chr16-23186868-G-A is described in ClinVar as [Benign]. Clinvar id is 1265535.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 rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4	c.317+280G>A		intron_variant	Intron 2 of 12	ENST00000300061.3	NP_001030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061.3	c.317+280G>A		intron_variant	Intron 2 of 12	1	NM_001039.4	ENSP00000300061.2

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31486 AN: 151832 Hom.: 3606 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.208 AC: 31534 AN: 151952 Hom.: 3624 Cov.: 32 AF XY: 0.208 AC XY: 15460 AN XY: 74266

Gnomad4 AFR AF: 0.118 AC: 0.118113 AN: 0.118113

Gnomad4 AMR AF: 0.307 AC: 0.306915 AN: 0.306915

Gnomad4 ASJ AF: 0.246 AC: 0.245817 AN: 0.245817

Gnomad4 EAS AF: 0.158 AC: 0.157976 AN: 0.157976

Gnomad4 SAS AF: 0.222 AC: 0.222315 AN: 0.222315

Gnomad4 FIN AF: 0.239 AC: 0.238953 AN: 0.238953

Gnomad4 NFE AF: 0.234 AC: 0.234298 AN: 0.234298

Gnomad4 OTH AF: 0.211 AC: 0.210701 AN: 0.210701

Alfa AF: 0.219 Hom.: 540

Bravo AF: 0.211

Asia WGS AF: 0.192 AC: 666 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9797088; hg19: chr16-23198189;