rs4800773

Positions:

• chr18-26865017-G-A
• chr18-26865017-G-C
• chr18-26865017-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.32+641C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,298 control chromosomes in the GnomAD database, including 10,615 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 0.37 (10615 hom., cov: 30)
• Consequence: AQP4 NM_001650.7 intron
• 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:26399): (AQP4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP4	NM_001650.7	c.32+641C>T		intron_variant		ENST00000383168.9	NP_001641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP4	ENST00000383168.9	c.32+641C>T		intron_variant		1	NM_001650.7	ENSP00000372654	P1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 55883 AN: 151190 Hom.: 10607 Cov.: 30

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.339

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.370 AC: 55931 AN: 151298 Hom.: 10615 Cov.: 30 AF XY: 0.365 AC XY: 26980 AN XY: 73856

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.337

Alfa AF: 0.347 Hom.: 5942

Bravo AF: 0.369

Asia WGS AF: 0.197 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.21

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: rs4800773; hg19: chr18-24444981;