Genetic Variant NM_001039.4:c.1176+210T>C (chr16-23210058-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001039.4(SCNN1G):c.1176+210T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,182 control chromosomes in the GnomAD database, including 44,912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.76 ( 44912 hom., cov: 33)

Consequence

SCNN1G
NM_001039.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.36

Publications

8 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 16-23210058-T-C is Benign according to our data. Variant chr16-23210058-T-C is described in ClinVar as [Benign]. Clinvar id is 1282630.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4 link	c.1176+210T>C		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.1176+210T>C		intron_variant	Intron 7 of 12	1	NM_001039.4	ENSP00000300061.2		P51170
ENSG00000260741	ENST00000563471.1 link	n.101+2946A>G		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.764

AC:

116103

AN:

152064

Hom.:

44878

Cov.:

show subpopulations

Gnomad AFR

AF:

0.650

Gnomad AMI

AF:

0.806

Gnomad AMR

AF:

0.830

Gnomad ASJ

AF:

0.864

Gnomad EAS

AF:

0.880

Gnomad SAS

AF:

0.845

Gnomad FIN

AF:

0.767

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.795

Gnomad OTH

AF:

0.795

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

GnomAD4 genome

AF:

0.763

AC:

116188

AN:

152182

Hom.:

44912

Cov.:

AF XY:

0.763

AC XY:

56776

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.650

AC:

26971

AN:

41492

American (AMR)

AF:

0.830

AC:

12686

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.864

AC:

2999

AN:

3470

East Asian (EAS)

AF:

0.880

AC:

4558

AN:

5178

South Asian (SAS)

AF:

0.846

AC:

4084

AN:

4826

European-Finnish (FIN)

AF:

0.767

AC:

8135

AN:

10610

Middle Eastern (MID)

AF:

0.857

AC:

252

AN:

294

European-Non Finnish (NFE)

AF:

0.795

AC:

54092

AN:

68010

Other (OTH)

AF:

0.794

AC:

1676

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1379

2757

4136

5514

6893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.761

Hom.:

9483

Bravo

AF:

0.767

Asia WGS

AF:

0.777

AC:

2700

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-0.93

CADD

Benign

1.1

(source)

DANN

Benign

0.44

PhyloP100

-1.4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_001039.4:c.1176+210T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over