Genetic Variant SCNN1G:c.317+18G>C (chr16-23186606-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001039.4(SCNN1G):c.317+18G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000709 in 1,605,946 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00073 ( 1 hom. )

Consequence

SCNN1G
NM_001039.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.773

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 16-23186606-G-C is Benign according to our data. Variant chr16-23186606-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1990292.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4 link	c.317+18G>C		intron_variant	Intron 2 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.317+18G>C		intron_variant	Intron 2 of 12	1	NM_001039.4	ENSP00000300061.2		P51170
ENSG00000285613	ENST00000648673.1 link	n.-211C>G		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000441

AC:

107

AN:

242446

AF XY:

0.000371

show subpopulations

Gnomad AFR exome

AF:

0.000252

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000568

Gnomad NFE exome

AF:

0.000904

Gnomad OTH exome

AF:

0.000497

GnomAD4 exome

AF:

0.000731

AC:

1062

AN:

1453664

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

515

AN XY:

723754

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

AC:

AN:

33406

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

44712

Gnomad4 ASJ exome

AF:

0.0000383

AC:

AN:

26122

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39694

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

86216

Gnomad4 FIN exome

AF:

0.0000620

AC:

AN:

48410

Gnomad4 NFE exome

AF:

0.000922

AC:

1023

AN:

1109092

Gnomad4 Remaining exome

AF:

0.000515

AC:

AN:

60250

Heterozygous variant carriers

114

170

227

284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.000499

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000144

AC:

0.00014439

AN:

0.00014439

Gnomad4 AMR

AF:

0.000131

AC:

0.000130719

AN:

0.000130719

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000985

AC:

0.000984946

AN:

0.000984946

Gnomad4 OTH

AF:

0.000473

AC:

0.000473037

AN:

0.000473037

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.000789

Hom.:

Bravo

AF:

0.000465

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 20, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.62

CADD

Benign

9.1

DANN

Benign

0.74

Mutation Taster

=100/0

polymorphism

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