rs3875089

Positions:

• chr18-26865469-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001650.7(AQP4):​c.32+189A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 740,602 control chromosomes in the GnomAD database, including 9,993 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 (3071 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6922 hom.)
• Consequence: AQP4 NM_001650.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP4	NM_001650.7	c.32+189A>G		intron_variant		ENST00000383168.9	NP_001641.1
AQP4-AS1	NR_026908.1	n.53+109T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP4	ENST00000383168.9	c.32+189A>G		intron_variant		1	NM_001650.7	ENSP00000372654	P1
AQP4-AS1	ENST00000578701.5	n.54+109T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28230 AN: 152016 Hom.: 3054 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.144 AC: 84653 AN: 588468 Hom.: 6922 Cov.: 7 AF XY: 0.143 AC XY: 45026 AN XY: 315858

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.0936

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.00168

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.186 AC: 28290 AN: 152134 Hom.: 3071 Cov.: 32 AF XY: 0.185 AC XY: 13793 AN XY: 74358

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.160

Alfa AF: 0.156 Hom.: 2864

Bravo AF: 0.184

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.90

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: rs3875089; hg19: chr18-24445433;