chr16-23380080-G-A

Variant names:

• chr16-23380080-G-A
• rs34618783
• NM_000336.3:c.1467-14G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000336.3(SCNN1B):​c.1467-14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,610,206 control chromosomes in the GnomAD database, including 914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (74 hom., cov: 32)
  • Exomes 𝑓: 0.028 (840 hom.)
• Consequence: SCNN1B NM_000336.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.669
• Publications: 7 publications found

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]

SCNN1B Gene-Disease associations (from GenCC):

• Liddle syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pseudohypoaldosteronism, type IB2, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
• bronchiectasis with or without elevated sweat chloride 1

  Inheritance: AD, SD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics
• pseudohypoaldosteronism, type IB1, autosomal recessive

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• Liddle syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 16-23380080-G-A is Benign according to our data. Variant chr16-23380080-G-A is described in ClinVar as Benign. ClinVar VariationId is 165170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0669 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000336.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1B	NM_000336.3	MANE Select	c.1467-14G>A		intron	N/A	NP_000327.2
	SCNN1B	NM_001410900.1		c.1359-14G>A		intron	N/A	NP_001397829.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1B	ENST00000343070.7	TSL:1 MANE Select	c.1467-14G>A		intron	N/A	ENSP00000345751.2
	SCNN1B	ENST00000307331.9	TSL:5	c.1602-14G>A		intron	N/A	ENSP00000302874.5
	SCNN1B	ENST00000568923.5	TSL:3	c.1386-14G>A		intron	N/A	ENSP00000456309.1

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3803 AN: 152044 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.00826

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0250

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.0728

Gnomad SAS AF: 0.0709

Gnomad FIN AF: 0.0409

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0249

Gnomad OTH AF: 0.0292

GnomAD2 exomes AF: 0.0377 AC: 9485 AN: 251446 AF XY: 0.0395

Gnomad AFR exome AF: 0.00757

Gnomad AMR exome AF: 0.0337

Gnomad ASJ exome AF: 0.0429

Gnomad EAS exome AF: 0.0748

Gnomad FIN exome AF: 0.0407

Gnomad NFE exome AF: 0.0268

Gnomad OTH exome AF: 0.0344

GnomAD4 exome AF: 0.0283 AC: 41203 AN: 1458044 Hom.: 840 Cov.: 30 AF XY: 0.0298 AC XY: 21646 AN XY: 725608

African (AFR) AF: 0.00709 AC: 237 AN: 33430

American (AMR) AF: 0.0313 AC: 1401 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 1067 AN: 26108

East Asian (EAS) AF: 0.0677 AC: 2684 AN: 39670

South Asian (SAS) AF: 0.0723 AC: 6233 AN: 86164

European-Finnish (FIN) AF: 0.0386 AC: 2060 AN: 53416

Middle Eastern (MID) AF: 0.0377 AC: 217 AN: 5750

European-Non Finnish (NFE) AF: 0.0230 AC: 25528 AN: 1108526

Other (OTH) AF: 0.0295 AC: 1776 AN: 60264

GnomAD4 genome AF: 0.0250 AC: 3801 AN: 152162 Hom.: 74 Cov.: 32 AF XY: 0.0262 AC XY: 1949 AN XY: 74380

African (AFR) AF: 0.00821 AC: 341 AN: 41518

American (AMR) AF: 0.0251 AC: 384 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 139 AN: 3470

East Asian (EAS) AF: 0.0730 AC: 377 AN: 5166

South Asian (SAS) AF: 0.0703 AC: 339 AN: 4820

European-Finnish (FIN) AF: 0.0409 AC: 434 AN: 10608

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0249 AC: 1690 AN: 67988

Other (OTH) AF: 0.0289 AC: 61 AN: 2108

Alfa AF: 0.0235 Hom.: 21

Bravo AF: 0.0231

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	1	Bronchiectasis with or without elevated sweat chloride 1 (1)
-	-	1	Liddle syndrome 1 (1)
-	-	1	Pseudohypoaldosteronism, type IB1, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.2
DANN	Benign	0.76
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34618783; hg19: chr16-23391401; COSMIC: COSV56304876;