rs72652281

Variant names:

• chr16-23302926-A-T
• rs72652281
• NM_000336.3:c.-9+489A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000336.3(SCNN1B):​c.-9+489A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 152,174 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.026 (62 hom., cov: 31)
• Consequence: SCNN1B NM_000336.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.824
• 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, PanelApp Australia, 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: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
• Liddle syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• bronchiectasis with or without elevated sweat chloride 1

  Inheritance: SD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-23302926-A-T is Benign according to our data. Variant chr16-23302926-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1326456.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0262 (3984/152174) while in subpopulation NFE AF = 0.0353 (2400/67994). AF 95% confidence interval is 0.0341. There are 62 homozygotes in GnomAd4. There are 1952 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 62 AR,AD,SD gene

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+489A>T		intron	N/A	NP_000327.2	B2R812
	SCNN1B	NM_001410900.1		c.-9+489A>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+489A>T		intron	N/A	ENSP00000345751.2	P51168-1
	SCNN1B	ENST00000962247.1		c.-9+489A>T		intron	N/A	ENSP00000632306.1
	SCNN1B	ENST00000890249.1		c.-34+489A>T		intron	N/A	ENSP00000560308.1

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3979 AN: 152056 Hom.: 61 Cov.: 31

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0353

Gnomad OTH AF: 0.0158

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

GnomAD4 genome AF: 0.0262 AC: 3984 AN: 152174 Hom.: 62 Cov.: 31 AF XY: 0.0262 AC XY: 1952 AN XY: 74406

African (AFR) AF: 0.0227 AC: 943 AN: 41526

American (AMR) AF: 0.0113 AC: 173 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5150

South Asian (SAS) AF: 0.00684 AC: 33 AN: 4824

European-Finnish (FIN) AF: 0.0311 AC: 330 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0353 AC: 2400 AN: 67994

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.0298 Hom.: 5

Bravo AF: 0.0235

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.81
CADD	Benign	1.0
DANN	Benign	0.63
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism

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: rs72652281; hg19: chr16-23314247;