16-23182544-A-G

Variant names:

• chr16-23182544-A-G
• rs5718
• ENST00000648673.1:n.194-973T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000648673.1(ENSG00000285613):​n.194-973T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,996 control chromosomes in the GnomAD database, including 26,505 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (26505 hom., cov: 35)
• Consequence: ENSG00000285613 ENST00000648673.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 14 publications found

Genes affected

ENSG00000285613 (HGNC:):

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]

SCNN1G Gene-Disease associations (from GenCC):

• Liddle syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• bronchiectasis with or without elevated sweat chloride 3

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• Liddle syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• pseudohypoaldosteronism, type IB1, autosomal recessive

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4	c.-314A>G		upstream_gene_variant		ENST00000300061.3	NP_001030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285613	ENST00000648673.1	n.194-973T>C		intron_variant	Intron 1 of 3
SCNN1G	ENST00000300061.3	c.-314A>G		upstream_gene_variant		1	NM_001039.4	ENSP00000300061.2

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87929 AN: 151884 Hom.: 26484 Cov.: 35

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.579 AC: 87970 AN: 151996 Hom.: 26505 Cov.: 35 AF XY: 0.584 AC XY: 43382 AN XY: 74304

African (AFR) AF: 0.427 AC: 17690 AN: 41476

American (AMR) AF: 0.711 AC: 10859 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2512 AN: 3468

East Asian (EAS) AF: 0.854 AC: 4391 AN: 5142

South Asian (SAS) AF: 0.799 AC: 3859 AN: 4828

European-Finnish (FIN) AF: 0.558 AC: 5910 AN: 10590

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.600 AC: 40753 AN: 67912

Other (OTH) AF: 0.604 AC: 1278 AN: 2116

Alfa AF: 0.573 Hom.: 3175

Bravo AF: 0.585

Asia WGS AF: 0.734 AC: 2551 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.3
DANN	Benign	0.36
PhyloP100		0.42
PromoterAI		-0.040	Neutral

Splicing

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

Other links and lift over

dbSNP: rs5718; hg19: chr16-23193865;