Genetic Variant NM_001039.4:c.1177-680G>A (chr16-23211354-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001039.4(SCNN1G):c.1177-680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,136 control chromosomes in the GnomAD database, including 3,537 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 3537 hom., cov: 32)

Consequence

SCNN1G
NM_001039.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.839

Publications

4 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:

ENSG00000260741 (HGNC:):

ENSG00000260741 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4 link	c.1177-680G>A		intron_variant	Intron 7 of 12	ENST00000300061.3	NP_001030.2	P51170A5X2V1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061.3 link	c.1177-680G>A		intron_variant	Intron 7 of 12	1	NM_001039.4	ENSP00000300061.2		P51170
ENSG00000260741	ENST00000563471.1 link	n.101+1650C>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32205

AN:

152018

Hom.:

3527

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.0609

Gnomad SAS

AF:

0.0741

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.208

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

GnomAD4 genome

AF:

0.212

AC:

32248

AN:

152136

Hom.:

3537

Cov.:

AF XY:

0.209

AC XY:

15521

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.247

AC:

10234

AN:

41510

American (AMR)

AF:

0.162

AC:

2483

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

786

AN:

3468

East Asian (EAS)

AF:

0.0606

AC:

314

AN:

5180

South Asian (SAS)

AF:

0.0742

AC:

358

AN:

4826

European-Finnish (FIN)

AF:

0.232

AC:

2459

AN:

10578

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.220

AC:

14927

AN:

67966

Other (OTH)

AF:

0.215

AC:

454

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1304

2609

3913

5218

6522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<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.:

495

Bravo

AF:

0.207

Asia WGS

AF:

0.110

AC:

381

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.080

(source)

DANN

Benign

0.33

PhyloP100

-0.84

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over