16-23303001-G-T

Variant names:

• chr16-23303001-G-T
• rs72652282
• NM_000336.3:c.-9+564G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000336.3(SCNN1B):​c.-9+564G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 152,220 control chromosomes in the GnomAD database, including 273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.034 (273 hom., cov: 31)
• Consequence: SCNN1B NM_000336.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23
• Publications: 0 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
• pseudohypoaldosteronism, type IB1, autosomal recessive

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• bronchiectasis with or without elevated sweat chloride 1

  Inheritance: SD, AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia
• Liddle syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-23303001-G-T is Benign according to our data. Variant chr16-23303001-G-T is described in ClinVar as Benign. ClinVar VariationId is 1678734.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1B	NM_000336.3	MANE Select	c.-9+564G>T		intron	N/A	NP_000327.2	B2R812
	SCNN1B	NM_001410900.1		c.-9+564G>T		intron	N/A	NP_001397829.1	H3BQ95

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1B	ENST00000343070.7	TSL:1 MANE Select	c.-9+564G>T		intron	N/A	ENSP00000345751.2	P51168-1
	SCNN1B	ENST00000962247.1		c.-9+564G>T		intron	N/A	ENSP00000632306.1
	SCNN1B	ENST00000890249.1		c.-34+564G>T		intron	N/A	ENSP00000560308.1

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 5100 AN: 152102 Hom.: 272 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0153

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

GnomAD4 genome AF: 0.0336 AC: 5111 AN: 152220 Hom.: 273 Cov.: 31 AF XY: 0.0321 AC XY: 2393 AN XY: 74436

African (AFR) AF: 0.117 AC: 4861 AN: 41514

American (AMR) AF: 0.0107 AC: 164 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68012

Other (OTH) AF: 0.0152 AC: 32 AN: 2110

Alfa AF: 0.0268 Hom.: 24

Bravo AF: 0.0385

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.90
DANN	Benign	0.87
PhyloP100		-1.2
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: rs72652282; hg19: chr16-23314322;