rs335929

chr18-26855623-A-Cchr18-26855623-A-G

Variant summary

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

The NM_001650.7(AQP4):c.*588T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 153,808 control chromosomes in the GnomAD database, including 2,423 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 0.16 (2399 hom., cov: 33)
  • Exomes 𝑓: 0.18 (24 hom.)
• Consequence: AQP4 NM_001650.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQP4	NM_001650.7	c.*588T>G		3_prime_UTR_variant	5/5	ENST00000383168.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP4	ENST00000383168.9	c.*588T>G		3_prime_UTR_variant	5/5	1	NM_001650.7	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23723 AN: 152078 Hom.: 2407 Cov.: 33

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.176 AC: 283 AN: 1612 Hom.: 24 Cov.: 0 AF XY: 0.172 AC XY: 150 AN XY: 874

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.226

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.156 AC: 23710 AN: 152196 Hom.: 2399 Cov.: 33 AF XY: 0.159 AC XY: 11865 AN XY: 74410

Gnomad4 AFR AF: 0.0416

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.167

Alfa AF: 0.189 Hom.: 4359

Bravo AF: 0.143

Asia WGS AF: 0.308 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.7
Dann	Benign	0.48

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: rs335929; hg19: chr18-24435587; COSMIC: COSV67219385; COSMIC: COSV67219385;