rs1058427

Positions:

• chr18-26855131-G-T

Variant summary

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

The NM_001650.7(AQP4):​c.*1080C>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 0.0874 in 152,252 control chromosomes in the GnomAD database, including 816 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 0.087 (816 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AQP4 NM_001650.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP4	NM_001650.7	c.*1080C>A		3_prime_UTR_variant	5/5	ENST00000383168.9	NP_001641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP4	ENST00000383168.9	c.*1080C>A		3_prime_UTR_variant	5/5	1	NM_001650.7	ENSP00000372654	P1

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13305 AN: 152134 Hom.: 816 Cov.: 33

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0946

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.000768

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0929

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0874 AC: 13303 AN: 152252 Hom.: 816 Cov.: 33 AF XY: 0.0872 AC XY: 6495 AN XY: 74444

Gnomad4 AFR AF: 0.0224

Gnomad4 AMR AF: 0.0945

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.0251

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.0919

Alfa AF: 0.112 Hom.: 495

Bravo AF: 0.0803

Asia WGS AF: 0.0170 AC: 61 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.69

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: rs1058427; hg19: chr18-24435095;