rs7956915

Positions:

• chr12-6361094-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001038.6(SCNN1A):​c.875+957T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,146 control chromosomes in the GnomAD database, including 21,164 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 0.52 (21164 hom., cov: 33)
• Consequence: SCNN1A NM_001038.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1A	NM_001038.6	c.875+957T>C		intron_variant		ENST00000228916.7	NP_001029.1
SCNN1A	NM_001159575.2	c.944+957T>C		intron_variant			NP_001153047.1
SCNN1A	NM_001159576.2	c.1052+957T>C		intron_variant			NP_001153048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1A	ENST00000228916.7	c.875+957T>C		intron_variant		1	NM_001038.6	ENSP00000228916	A2

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79575 AN: 152028 Hom.: 21142 Cov.: 33

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.523 AC: 79634 AN: 152146 Hom.: 21164 Cov.: 33 AF XY: 0.525 AC XY: 39026 AN XY: 74368

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.556

Alfa AF: 0.540 Hom.: 10146

Bravo AF: 0.529

Asia WGS AF: 0.645 AC: 2244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.1
DANN	Benign	0.59

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: rs7956915; hg19: chr12-6470260;