rs5729

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001039.4(SCNN1G):c.*606T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 161,576 control chromosomes in the GnomAD database, including 3,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3528 hom., cov: 33)

Exomes 𝑓: 0.12 ( 82 hom. )

Consequence

SCNN1G
NM_001039.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.388

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

Liddle syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
bronchiectasis with or without elevated sweat chloride 3
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
Liddle syndrome 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
pseudohypoaldosteronism, type IB1, autosomal recessive
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

SCNN1G links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-23216075-T-A is Benign according to our data. Variant chr16-23216075-T-A is described in ClinVar as Benign. ClinVar VariationId is 318370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4 link	c.*606T>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000300061.3	NP_001030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061.3 link	c.*606T>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_001039.4	ENSP00000300061.2

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32186

AN:

152046

Hom.:

3519

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.0613

Gnomad SAS

AF:

0.0741

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.209

GnomAD4 exome

AF:

0.117

AC:

1102

AN:

9412

Hom.:

Cov.:

AF XY:

0.112

AC XY:

531

AN XY:

4744

show subpopulations

African (AFR)

AF:

0.188

AC:

AN:

American (AMR)

AF:

0.0864

AC:

159

AN:

1840

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

AN:

East Asian (EAS)

AF:

0.0128

AC:

AN:

390

South Asian (SAS)

AF:

0.0336

AC:

AN:

804

European-Finnish (FIN)

AF:

0.100

AC:

AN:

200

Middle Eastern (MID)

AF:

0.100

AC:

AN:

European-Non Finnish (NFE)

AF:

0.146

AC:

818

AN:

5602

Other (OTH)

AF:

0.118

AC:

AN:

408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

122

163

204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.212

AC:

32224

AN:

152164

Hom.:

3528

Cov.:

AF XY:

0.208

AC XY:

15504

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.246

AC:

10210

AN:

41496

American (AMR)

AF:

0.162

AC:

2485

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

787

AN:

3472

East Asian (EAS)

AF:

0.0611

AC:

317

AN:

5188

South Asian (SAS)

AF:

0.0742

AC:

358

AN:

4828

European-Finnish (FIN)

AF:

0.232

AC:

2451

AN:

10582

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.220

AC:

14930

AN:

67990

Other (OTH)

AF:

0.216

AC:

454

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1326

2652

3978

5304

6630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.226

Hom.:

511

Bravo

AF:

0.207

Asia WGS

AF:

0.110

AC:

381

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

May 15, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Pseudohypoaldosteronism, type IB1, autosomal recessive

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Liddle syndrome 2

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

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

-0.89

CADD

Benign

1.1

(source)

DANN

Benign

0.60

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over