16-23302926-A-T

Position:

• chr16-23302926-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.81).
• 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 id 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 62 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1B	NM_000336.3	c.-9+489A>T		intron_variant		ENST00000343070.7	NP_000327.2
SCNN1B	NM_001410900.1	c.-9+489A>T		intron_variant			NP_001397829.1
SCNN1B	XM_011545913.3	c.-1+489A>T		intron_variant			XP_011544215.1
SCNN1B	XM_017023525.2	c.49+19122A>T		intron_variant			XP_016879014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1B	ENST00000343070.7	c.-9+489A>T		intron_variant		1	NM_000336.3	ENSP00000345751	P1
SCNN1B	ENST00000569789.1	n.178+19122A>T		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.0227

Gnomad4 AMR AF: 0.0113

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.0311

Gnomad4 NFE AF: 0.0353

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0298 Hom.: 5

Bravo AF: 0.0235

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely 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	-0.81
CADD	Benign	1.0
DANN	Benign	0.63

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: rs72652281; hg19: chr16-23314247;