NM_001039.4:c.-44-247C>T

Variant names:

• chr16-23185981-C-T
• rs13306657
• NM_001039.4:c.-44-247C>T

Variant summary

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

The NM_001039.4(SCNN1G):​c.-44-247C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 151,964 control chromosomes in the GnomAD database, including 3,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3407 hom., cov: 33)
• Consequence: SCNN1G NM_001039.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0780

Genes affected

SCNN1G (HGNC:10602): (sodium channel epithelial 1 subunit gamma) 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 gamma subunit, and mutations in this gene have been associated with Liddle syndrome. [provided by RefSeq, Apr 2009]

ENSG00000285613 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-23185981-C-T is Benign according to our data. Variant chr16-23185981-C-T is described in ClinVar as [Benign]. Clinvar id is 1283927.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4	c.-44-247C>T		intron_variant	Intron 1 of 12	ENST00000300061.3	NP_001030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061.3	c.-44-247C>T		intron_variant	Intron 1 of 12	1	NM_001039.4	ENSP00000300061.2
ENSG00000285613	ENST00000648673.1	n.193+222G>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29518 AN: 151844 Hom.: 3390 Cov.: 33

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.195 AC: 29561 AN: 151964 Hom.: 3407 Cov.: 33 AF XY: 0.196 AC XY: 14526 AN XY: 74300

Gnomad4 AFR AF: 0.0774

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.201

Alfa AF: 0.216 Hom.: 516

Bravo AF: 0.196

Asia WGS AF: 0.181 AC: 628 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.4
DANN	Benign	0.90

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: rs13306657; hg19: chr16-23197302;