rs72557968

chr18-26862263-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001650.7(AQP4):c.366G>A(p.Gln122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 1,614,164 control chromosomes in the GnomAD database, including 706 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 0.018 (44 hom., cov: 32)
  • Exomes 𝑓: 0.022 (662 hom.)
• Consequence: AQP4 NM_001650.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP7: Synonymous conserved (PhyloP=3.15 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQP4	NM_001650.7	c.366G>A	p.Gln122=	synonymous_variant	2/5	ENST00000383168.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP4	ENST00000383168.9	c.366G>A	p.Gln122=	synonymous_variant	2/5	1	NM_001650.7	P1

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2736 AN: 152168 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.00989

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.0358

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.0263 AC: 6620 AN: 251376 Hom.: 189 AF XY: 0.0310 AC XY: 4208 AN XY: 135892

Gnomad AFR exome AF: 0.00979

Gnomad AMR exome AF: 0.00827

Gnomad ASJ exome AF: 0.0241

Gnomad EAS exome AF: 0.00234

Gnomad SAS exome AF: 0.0951

Gnomad FIN exome AF: 0.0366

Gnomad NFE exome AF: 0.0180

Gnomad OTH exome AF: 0.0220

GnomAD4 exome AF: 0.0223 AC: 32615 AN: 1461878 Hom.: 662 Cov.: 31 AF XY: 0.0246 AC XY: 17875 AN XY: 727242

Gnomad4 AFR exome AF: 0.00938

Gnomad4 AMR exome AF: 0.00823

Gnomad4 ASJ exome AF: 0.0222

Gnomad4 EAS exome AF: 0.00169

Gnomad4 SAS exome AF: 0.0906

Gnomad4 FIN exome AF: 0.0350

Gnomad4 NFE exome AF: 0.0182

Gnomad4 OTH exome AF: 0.0192

GnomAD4 genome AF: 0.0179 AC: 2733 AN: 152286 Hom.: 44 Cov.: 32 AF XY: 0.0205 AC XY: 1523 AN XY: 74450

Gnomad4 AFR AF: 0.00989

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.00387

Gnomad4 SAS AF: 0.0935

Gnomad4 FIN AF: 0.0358

Gnomad4 NFE AF: 0.0175

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0179 Hom.: 11

Bravo AF: 0.0139

Asia WGS AF: 0.0410 AC: 144 AN: 3478

EpiCase AF: 0.0185

EpiControl AF: 0.0176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	13
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs72557968; hg19: chr18-24442227;