chr16-23348780-G-A

Position:

• chr16-23348780-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_000336.3(SCNN1B):​c.181G>A​(p.Ala61Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,614,144 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: SCNN1B NM_000336.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.147

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007142335).
• BP6: Variant 16-23348780-G-A is Benign according to our data. Variant chr16-23348780-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 789832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00126 (192/152280) while in subpopulation AFR AF= 0.00445 (185/41566). AF 95% confidence interval is 0.00393. There are 0 homozygotes in gnomad4. There are 81 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1B	NM_000336.3	c.181G>A	p.Ala61Thr	missense_variant	2/13	ENST00000343070.7	NP_000327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000343070.7	c.181G>A	p.Ala61Thr	missense_variant	2/13	1	NM_000336.3	ENSP00000345751.2

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 193 AN: 152162 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000354 AC: 89 AN: 251332 Hom.: 0 AF XY: 0.000206 AC XY: 28 AN XY: 135846

Gnomad AFR exome AF: 0.00492

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000128 AC: 187 AN: 1461864 Hom.: 1 Cov.: 32 AF XY: 0.000109 AC XY: 79 AN XY: 727228

Gnomad4 AFR exome AF: 0.00460

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.000248

GnomAD4 genome AF: 0.00126 AC: 192 AN: 152280 Hom.: 0 Cov.: 31 AF XY: 0.00109 AC XY: 81 AN XY: 74452

Gnomad4 AFR AF: 0.00445

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000272 Hom.: 0

Bravo AF: 0.00147

ESP6500AA AF: 0.00341 AC: 15

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000478 AC: 58

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 11, 2021	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	Nov 03, 2022	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 19, 2023

- -

SCNN1B-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 16, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.80
DANN	Benign	0.96
DEOGEN2	Benign	0.26	T;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.056	N
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.0071	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L;.;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.020	D;D;D;D
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.39	B;.;.;.
Vest4		0.077
MVP		0.43
MPC		0.22
ClinPred		0.016	T
GERP RS		-1.9
Varity_R		0.059
gMVP		0.46

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: rs72654321; hg19: chr16-23360101; COSMIC: COSV56303664; COSMIC: COSV56303664;