16-23301864-G-A

Position:

• chr16-23301864-G-A

Variant summary

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

The XM_017023525.2(SCNN1B):​c.49+18060G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,150 control chromosomes in the GnomAD database, including 2,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (2946 hom., cov: 31)
• Consequence: SCNN1B XM_017023525.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.207

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=-0.97).
• BP6: Variant 16-23301864-G-A is Benign according to our data. Variant chr16-23301864-G-A is described in ClinVar as [Benign]. Clinvar id is 1233203.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1B	XM_017023525.2	c.49+18060G>A		intron_variant			XP_016879014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000569789.1	n.178+18060G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19044 AN: 152032 Hom.: 2929 Cov.: 31

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0452

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00788

Gnomad FIN AF: 0.0309

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0824

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

GnomAD4 genome AF: 0.126 AC: 19098 AN: 152150 Hom.: 2946 Cov.: 31 AF XY: 0.122 AC XY: 9052 AN XY: 74384

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.0451

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00810

Gnomad4 FIN AF: 0.0309

Gnomad4 NFE AF: 0.0364

Gnomad4 OTH AF: 0.0825

Alfa AF: 0.0875 Hom.: 428

Bravo AF: 0.137

Asia WGS AF: 0.0330 AC: 115 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 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34241435; hg19: chr16-23313185;