rs2106374

Positions:

• chr16-23294425-T-C

Variant summary

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

The XM_017023525.2(SCNN1B):​c.49+10621T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,536 control chromosomes in the GnomAD database, including 2,530 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 0.18 (2530 hom., cov: 30)
• Consequence: SCNN1B XM_017023525.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

Genes affected

SCNN1B (HGNC:10600): (sodium channel epithelial 1 subunit beta) 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 beta subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), and Liddle syndrome. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1B	XM_017023525.2	c.49+10621T>C		intron_variant			XP_016879014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000569789.1	n.178+10621T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26714 AN: 151418 Hom.: 2523 Cov.: 30

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0903

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.176 AC: 26719 AN: 151536 Hom.: 2530 Cov.: 30 AF XY: 0.179 AC XY: 13259 AN XY: 74036

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.224

Alfa AF: 0.193 Hom.: 2591

Bravo AF: 0.173

Asia WGS AF: 0.278 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.89

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2106374; hg19: chr16-23305746;