chr12-6370126-A-C

Position:

• chr12-6370126-A-C

Variant summary

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

The NM_001038.6(SCNN1A):​c.416+4242T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,028 control chromosomes in the GnomAD database, including 16,306 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 0.42 (16306 hom., cov: 32)
• Consequence: SCNN1A NM_001038.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926

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]

LOC105369626 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1A	NM_001038.6	c.416+4242T>G		intron_variant		ENST00000228916.7	NP_001029.1
LOC105369626	XR_931591.3	n.689-634A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1A	ENST00000228916.7	c.416+4242T>G		intron_variant		1	NM_001038.6	ENSP00000228916	A2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63427 AN: 151910 Hom.: 16317 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.417 AC: 63414 AN: 152028 Hom.: 16306 Cov.: 32 AF XY: 0.410 AC XY: 30484 AN XY: 74296

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.488

Alfa AF: 0.546 Hom.: 15052

Bravo AF: 0.399

Asia WGS AF: 0.231 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.78

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: rs10849446; hg19: chr12-6479292;