12-6349108-G-C

Position:

• chr12-6349108-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001038.6(SCNN1A):​c.1497+56C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,602,410 control chromosomes in the GnomAD database, including 40,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3113 hom., cov: 31)
  • Exomes 𝑓: 0.22 (37304 hom.)
• Consequence: SCNN1A NM_001038.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.342

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]

LOC107984500 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-6349108-G-C is Benign according to our data. Variant chr12-6349108-G-C is described in ClinVar as [Benign]. Clinvar id is 1271585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCNN1A	NM_001038.6	c.1497+56C>G		intron_variant		ENST00000228916.7
LOC107984500	XR_007063191.1	n.87+841G>C		intron_variant, non_coding_transcript_variant
SCNN1A	NM_001159575.2	c.1566+56C>G		intron_variant
SCNN1A	NM_001159576.2	c.1674+56C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCNN1A	ENST00000228916.7	c.1497+56C>G		intron_variant		1	NM_001038.6	A2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30179 AN: 151914 Hom.: 3109 Cov.: 31

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.224 AC: 324898 AN: 1450378 Hom.: 37304 Cov.: 29 AF XY: 0.226 AC XY: 163077 AN XY: 722360

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.284

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.199 AC: 30193 AN: 152032 Hom.: 3113 Cov.: 31 AF XY: 0.201 AC XY: 14904 AN XY: 74322

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.185

Alfa AF: 0.128 Hom.: 264

Bravo AF: 0.187

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.49
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs3764874; hg19: chr12-6458274;