rs1058424

Positions:

• chr18-26855581-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001650.7(AQP4):​c.*630T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 153,174 control chromosomes in the GnomAD database, including 3,238 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 0.19 (3228 hom., cov: 33)
  • Exomes 𝑓: 0.13 (10 hom.)
• Consequence: AQP4 NM_001650.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

Genes affected

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]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQP4	NM_001650.7	c.*630T>A		3_prime_UTR_variant	5/5	ENST00000383168.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP4	ENST00000383168.9	c.*630T>A		3_prime_UTR_variant	5/5	1	NM_001650.7	P1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28388 AN: 152030 Hom.: 3214 Cov.: 33

Gnomad AFR AF: 0.0963

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.129 AC: 132 AN: 1026 Hom.: 10 Cov.: 0 AF XY: 0.130 AC XY: 76 AN XY: 584

Gnomad4 AMR exome AF: 0.121

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.0625

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.0957

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.187 AC: 28414 AN: 152148 Hom.: 3228 Cov.: 33 AF XY: 0.189 AC XY: 14025 AN XY: 74374

Gnomad4 AFR AF: 0.0960

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.227

Alfa AF: 0.185 Hom.: 351

Bravo AF: 0.197

Asia WGS AF: 0.301 AC: 1049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.64
DANN	Benign	0.79

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: rs1058424; hg19: chr18-24435545; COSMIC: COSV67218769; COSMIC: COSV67218769;