16-23302732-T-C

Position:

• chr16-23302732-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000336.3(SCNN1B):​c.-9+295T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,884 control chromosomes in the GnomAD database, including 8,278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (8278 hom., cov: 31)
• Consequence: SCNN1B NM_000336.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.17

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-23302732-T-C is Benign according to our data. Variant chr16-23302732-T-C is described in ClinVar as [Benign]. Clinvar id is 1261922.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1B	NM_000336.3	c.-9+295T>C		intron_variant		ENST00000343070.7	NP_000327.2
SCNN1B	NM_001410900.1	c.-9+295T>C		intron_variant			NP_001397829.1
SCNN1B	XM_011545913.3	c.-1+295T>C		intron_variant			XP_011544215.1
SCNN1B	XM_017023525.2	c.49+18928T>C		intron_variant			XP_016879014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000343070.7	c.-9+295T>C		intron_variant		1	NM_000336.3	ENSP00000345751	P1
SCNN1B	ENST00000569789.1	n.178+18928T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46536 AN: 151766 Hom.: 8245 Cov.: 31

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.307 AC: 46608 AN: 151884 Hom.: 8278 Cov.: 31 AF XY: 0.306 AC XY: 22709 AN XY: 74230

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.311

Alfa AF: 0.189 Hom.: 605

Bravo AF: 0.314

Asia WGS AF: 0.314 AC: 1089 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs57825792; hg19: chr16-23314053;