chr18-26855854-C-T

Position:

• chr18-26855854-C-T

Variant summary

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

The NM_001650.7(AQP4):​c.*357G>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 0.311 in 303,576 control chromosomes in the GnomAD database, including 15,445 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 0.31 (7603 hom., cov: 32)
  • Exomes 𝑓: 0.32 (7842 hom.)
• Consequence: AQP4 NM_001650.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP4	NM_001650.7	c.*357G>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.*357G>A		3_prime_UTR_variant	5/5	1	NM_001650.7	ENSP00000372654.4

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46544 AN: 151754 Hom.: 7583 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.316 AC: 47872 AN: 151704 Hom.: 7842 Cov.: 0 AF XY: 0.309 AC XY: 25165 AN XY: 81498

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.481

Gnomad4 ASJ exome AF: 0.293

Gnomad4 EAS exome AF: 0.408

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.282

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.321

GnomAD4 genome AF: 0.307 AC: 46605 AN: 151872 Hom.: 7603 Cov.: 32 AF XY: 0.306 AC XY: 22706 AN XY: 74190

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.338

Alfa AF: 0.320 Hom.: 15936

Bravo AF: 0.324

Asia WGS AF: 0.346 AC: 1206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.49

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: rs3763043; hg19: chr18-24435818;