Variant 16-23186241-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001039.4(SCNN1G):c.-31A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,610,944 control chromosomes in the GnomAD database, including 44,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3589 hom., cov: 33)

Exomes 𝑓: 0.23 ( 41029 hom. )

Consequence

SCNN1G
NM_001039.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.38

Variant links:

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 links:

ENSG00000285613 (HGNC:):

ENSG00000285613 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 16-23186241-A-G is Benign according to our data. Variant chr16-23186241-A-G is described in ClinVar as [Benign]. Clinvar id is 318344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23186241-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1G	NM_001039.4 link	c.-31A>G		5_prime_UTR_variant	2/13	ENST00000300061.3	NP_001030.2	P51170A5X2V1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061 link	c.-31A>G		5_prime_UTR_variant	2/13	1	NM_001039.4	ENSP00000300061.2		P51170
ENSG00000285613	ENST00000648673.1 link	n.155T>C		non_coding_transcript_exon_variant	1/4

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31430

AN:

151950

Hom.:

3571

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.210

GnomAD3 exomes

AF:

0.243

AC:

60641

AN:

249856

Hom.:

8009

AF XY:

0.238

AC XY:

32170

AN XY:

135280

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.395

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.152

Gnomad SAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.246

Gnomad NFE exome

AF:

0.232

Gnomad OTH exome

AF:

0.239

GnomAD4 exome

AF:

0.233

AC:

339626

AN:

1458876

Hom.:

41029

Cov.:

AF XY:

0.233

AC XY:

169012

AN XY:

725894

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.391

Gnomad4 ASJ exome

AF:

0.249

Gnomad4 EAS exome

AF:

0.145

Gnomad4 SAS exome

AF:

0.231

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.233

Gnomad4 OTH exome

AF:

0.231

GnomAD4 genome

AF:

0.207

AC:

31478

AN:

152068

Hom.:

3589

Cov.:

AF XY:

0.208

AC XY:

15453

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.307

Gnomad4 ASJ

AF:

0.246

Gnomad4 EAS

AF:

0.159

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.238

Gnomad4 NFE

AF:

0.234

Gnomad4 OTH

AF:

0.209

Alfa

AF:

0.230

Hom.:

1125

Bravo

AF:

0.211

Asia WGS

AF:

0.193

AC:

668

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Pseudohypoaldosteronism, type IB1, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Liddle syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.0

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over