rs162007

Variant names:

• chr18-26865883-G-A
• rs162007
• ENST00000578701.5:n.54+523G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-26865883-G-A
• chr18-26865883-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000578701.5(AQP4-AS1):​n.54+523G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 614,086 control chromosomes in the GnomAD database, including 13,808 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 0.17 (2569 hom., cov: 33)
  • Exomes 𝑓: 0.21 (11239 hom.)
• Consequence: AQP4-AS1 ENST00000578701.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.627

Genes affected

AQP4-AS1 (HGNC:26399): (AQP4 antisense RNA 1)

AQP4 (HGNC:637): (aquaporin 4) This gene encodes a member of the aquaporin family of intrinsic membrane proteins that function as water-selective channels in the plasma membranes of many cells. This protein is the predominant aquaporin found in brain and has an important role in brain water homeostasis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. Additional isoforms, resulting from the use of alternative in-frame translation initiation codons, have also been described. Recent studies provided evidence for translational readthrough in this gene, and expression of C-terminally extended isoforms via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Jun 2018]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP4	NM_001650.7	c.-194C>T		upstream_gene_variant		ENST00000383168.9	NP_001641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP4	ENST00000383168.9	c.-194C>T		upstream_gene_variant		1	NM_001650.7	ENSP00000372654.4

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26477 AN: 151474 Hom.: 2575 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.194

GnomAD4 exome AF: 0.213 AC: 98650 AN: 462494 Hom.: 11239 AF XY: 0.219 AC XY: 53465 AN XY: 244314

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.368

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.201

GnomAD4 genome AF: 0.175 AC: 26459 AN: 151592 Hom.: 2569 Cov.: 33 AF XY: 0.177 AC XY: 13106 AN XY: 74070

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.191

Alfa AF: 0.190 Hom.: 2724

Bravo AF: 0.164

Asia WGS AF: 0.292 AC: 1013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs162007; hg19: chr18-24445847;