rs35074083

chr16-23380404-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000336.3(SCNN1B):c.1543-17C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00822 in 1,614,002 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0083 (56 hom.)
• Consequence: SCNN1B NM_000336.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.164

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-23380404-C-T is Benign according to our data. Variant chr16-23380404-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23380404-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00704 (1072/152330) while in subpopulation NFE AF= 0.0103 (700/68024). AF 95% confidence interval is 0.00966. There are 10 homozygotes in gnomad4. There are 518 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCNN1B	NM_000336.3	c.1543-17C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000343070.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCNN1B	ENST00000343070.7	c.1543-17C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000336.3	P1

Frequencies

GnomAD3 genomes AF: 0.00705 AC: 1073 AN: 152212 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00642 AC: 1611 AN: 250898 Hom.: 6 AF XY: 0.00649 AC XY: 880 AN XY: 135660

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00275

Gnomad ASJ exome AF: 0.00328

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00111

Gnomad FIN exome AF: 0.0132

Gnomad NFE exome AF: 0.00974

Gnomad OTH exome AF: 0.00669

GnomAD4 exome AF: 0.00835 AC: 12201 AN: 1461672 Hom.: 56 Cov.: 32 AF XY: 0.00830 AC XY: 6038 AN XY: 727144

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.00362

Gnomad4 ASJ exome AF: 0.00310

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00108

Gnomad4 FIN exome AF: 0.0125

Gnomad4 NFE exome AF: 0.00963

Gnomad4 OTH exome AF: 0.00679

GnomAD4 genome AF: 0.00704 AC: 1072 AN: 152330 Hom.: 10 Cov.: 32 AF XY: 0.00695 AC XY: 518 AN XY: 74482

Gnomad4 AFR AF: 0.00176

Gnomad4 AMR AF: 0.00601

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.0103

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00924 Hom.: 3

Bravo AF: 0.00623

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 12, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 22, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 04, 2021	This variant is associated with the following publications: (PMID: 15661075) -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.57
Dann	Benign	0.61

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: rs35074083; hg19: chr16-23391725;