rs238547

Variant names:

• chr16-23348878-T-C
• rs238547
• NM_000336.3:c.279T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-23348878-T-C
• chr16-23348878-T-A
• chr16-23348878-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000336.3(SCNN1B):​c.279T>C​(p.Pro93Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,613,704 control chromosomes in the GnomAD database, including 294,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (36163 hom., cov: 30)
  • Exomes 𝑓: 0.58 (258772 hom.)
• Consequence: SCNN1B NM_000336.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:16
• Conservation: PhyloP100: -3.32
• Publications: 27 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 16-23348878-T-C is Benign according to our data. Variant chr16-23348878-T-C is described in ClinVar as Benign. ClinVar VariationId is 165167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 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.279T>C	p.Pro93Pro	synonymous	Exon 2 of 13	NP_000327.2	B2R812
	SCNN1B	NM_001410900.1		c.279T>C	p.Pro93Pro	synonymous	Exon 2 of 12	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.279T>C	p.Pro93Pro	synonymous	Exon 2 of 13	ENSP00000345751.2	P51168-1
	SCNN1B	ENST00000307331.9	TSL:5	c.414T>C	p.Pro138Pro	synonymous	Exon 3 of 14	ENSP00000302874.5	P51168-2
	SCNN1B	ENST00000962247.1		c.279T>C	p.Pro93Pro	synonymous	Exon 2 of 13	ENSP00000632306.1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101178 AN: 151872 Hom.: 36106 Cov.: 30

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.636

GnomAD2 exomes AF: 0.621 AC: 155174 AN: 249886 AF XY: 0.629

Gnomad AFR exome AF: 0.914

Gnomad AMR exome AF: 0.435

Gnomad ASJ exome AF: 0.582

Gnomad EAS exome AF: 0.984

Gnomad FIN exome AF: 0.501

Gnomad NFE exome AF: 0.558

Gnomad OTH exome AF: 0.600

GnomAD4 exome AF: 0.584 AC: 853991 AN: 1461714 Hom.: 258772 Cov.: 60 AF XY: 0.590 AC XY: 428734 AN XY: 727148

African (AFR) AF: 0.918 AC: 30730 AN: 33480

American (AMR) AF: 0.441 AC: 19733 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 15113 AN: 26136

East Asian (EAS) AF: 0.988 AC: 39241 AN: 39700

South Asian (SAS) AF: 0.785 AC: 67697 AN: 86256

European-Finnish (FIN) AF: 0.501 AC: 26748 AN: 53414

Middle Eastern (MID) AF: 0.716 AC: 4130 AN: 5768

European-Non Finnish (NFE) AF: 0.552 AC: 613593 AN: 1111854

Other (OTH) AF: 0.613 AC: 37006 AN: 60386

GnomAD4 genome AF: 0.666 AC: 101278 AN: 151990 Hom.: 36163 Cov.: 30 AF XY: 0.668 AC XY: 49640 AN XY: 74282

African (AFR) AF: 0.905 AC: 37535 AN: 41464

American (AMR) AF: 0.502 AC: 7662 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1990 AN: 3472

East Asian (EAS) AF: 0.985 AC: 5069 AN: 5146

South Asian (SAS) AF: 0.814 AC: 3914 AN: 4808

European-Finnish (FIN) AF: 0.512 AC: 5401 AN: 10558

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37508 AN: 67956

Other (OTH) AF: 0.639 AC: 1349 AN: 2110

Alfa AF: 0.598 Hom.: 60270

Bravo AF: 0.674

Asia WGS AF: 0.896 AC: 3114 AN: 3478

EpiCase AF: 0.568

EpiControl AF: 0.581

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	3	not provided (3)
-	-	2	Bronchiectasis with or without elevated sweat chloride 1 (2)
-	-	2	Liddle syndrome 1 (2)
-	-	2	Pseudohypoaldosteronism, type IB1, autosomal recessive (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.28
DANN	Benign	0.58
PhyloP100		-3.3
PromoterAI		-0.022	Neutral
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: rs238547; hg19: chr16-23360199; COSMIC: COSV108137889;