chr12-6375636-G-A

Position:

chr12-6375636-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001159575.2(SCNN1A):c.16-799C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,489,374 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0026 ( 5 hom. )

Consequence

SCNN1A
NM_001159575.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.405

Variant links:

Genes affected

SCNN1A (HGNC:10599): (sodium channel epithelial 1 subunit alpha) 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 alpha subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), a rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2009]

SCNN1A links:

LTBR (HGNC:6718): (lymphotoxin beta receptor) This gene encodes a member of the tumor necrosis factor receptor superfamily. The major ligands of this receptor include lymphotoxin alpha/beta and tumor necrosis factor ligand superfamily member 14. The encoded protein plays a role in signalling during the development of lymphoid and other organs, lipid metabolism, immune response, and programmed cell death. Activity of this receptor has also been linked to carcinogenesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2012]

LTBR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-6375636-G-A is Benign according to our data. Variant chr12-6375636-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 310162.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00248 (378/152264) while in subpopulation AMR AF= 0.00889 (136/15296). AF 95% confidence interval is 0.00767. There are 1 homozygotes in gnomad4. There are 191 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
SCNN1A	NM_001159575.2 link	c.16-799C>T	intron_variant	NP_001153047.1	P37088-6
LTBR	NM_001270987.2 link	c.39+42G>A	intron_variant	NP_001257916.1	P36941-2
LTBR	NM_001414309.1 link	c.39+42G>A	intron_variant	NP_001401238.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
SCNN1A	ENST00000543768.1 link	c.16-799C>T	intron_variant	2	ENSP00000438739.1	P37088-6
LTBR	ENST00000539925.5 link	c.39+42G>A	intron_variant	2	ENSP00000440875.1	P36941-2
SCNN1A	ENST00000536788.1 link	c.10-799C>T	intron_variant	4	ENSP00000443434.1	F5H5F8

Frequencies

GnomAD3 genomes

AF:

0.00248

AC:

378

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00890

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00293

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00213

AC:

198

AN:

93108

Hom.:

AF XY:

0.00209

AC XY:

106

AN XY:

50644

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.00422

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000302

Gnomad FIN exome

AF:

0.000285

Gnomad NFE exome

AF:

0.00305

Gnomad OTH exome

AF:

0.00170

GnomAD4 exome

AF:

0.00260

AC:

3474

AN:

1337110

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

1647

AN XY:

655322

show subpopulations

Gnomad4 AFR exome

AF:

0.000611

Gnomad4 AMR exome

AF:

0.00400

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000121

Gnomad4 FIN exome

AF:

0.000280

Gnomad4 NFE exome

AF:

0.00306

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00248

AC:

378

AN:

152264

Hom.:

Cov.:

AF XY:

0.00257

AC XY:

191

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000915

Gnomad4 AMR

AF:

0.00889

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00293

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00179

Hom.:

Bravo

AF:

0.00273

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Pseudohypoaldosteronism, type IB1, autosomal recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Bronchiectasis with or without elevated sweat chloride 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.4

DANN

Benign

0.77

Splicing

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