16-23378880-G-C

Position:

• chr16-23378880-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000336.3(SCNN1B):​c.1466+113G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 988,058 control chromosomes in the GnomAD database, including 159,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (29223 hom., cov: 30)
  • Exomes 𝑓: 0.55 (130554 hom.)
• Consequence: SCNN1B NM_000336.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0720

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 16-23378880-G-C is Benign according to our data. Variant chr16-23378880-G-C is described in ClinVar as [Benign]. Clinvar id is 1249214.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCNN1B	NM_000336.3	c.1466+113G>C		intron_variant		ENST00000343070.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCNN1B	ENST00000343070.7	c.1466+113G>C		intron_variant		1	NM_000336.3	P1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91477 AN: 151786 Hom.: 29163 Cov.: 30

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.587

GnomAD4 exome AF: 0.547 AC: 457034 AN: 836154 Hom.: 130554 AF XY: 0.549 AC XY: 238154 AN XY: 434128

Gnomad4 AFR exome AF: 0.770

Gnomad4 AMR exome AF: 0.736

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.883

Gnomad4 SAS exome AF: 0.686

Gnomad4 FIN exome AF: 0.473

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.558

GnomAD4 genome AF: 0.603 AC: 91604 AN: 151904 Hom.: 29223 Cov.: 30 AF XY: 0.606 AC XY: 44998 AN XY: 74244

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.592

Alfa AF: 0.371 Hom.: 849

Bravo AF: 0.625

Asia WGS AF: 0.762 AC: 2649 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.8
DANN	Benign	0.48

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: rs2303153; hg19: chr16-23390201; COSMIC: COSV56308340;