dbSNP rs162007: AQP4-AS1:n.54+523G>A (chr18-26865883-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000578701.5(AQP4-AS1):n.54+523G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 614,086 control chromosomes in the GnomAD database, including 13,808 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 0.17 ( 2569 hom., cov: 33)

Exomes 𝑓: 0.21 ( 11239 hom. )

Consequence

AQP4-AS1
ENST00000578701.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.627

Publications

11 publications found

Variant links:

Genes affected

AQP4-AS1 (HGNC:26399): (AQP4 antisense RNA 1)

AQP4-AS1 links:

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 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
megalencephalic leukoencephalopathy with subcortical cysts 4, remitting
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
neuromyelitis optica
Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

AQP4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP4	NM_001650.7 link	c.-194C>T		upstream_gene_variant		ENST00000383168.9	NP_001641.1	P55087-1F1DSG4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP4	ENST00000383168.9 link	c.-194C>T		upstream_gene_variant		1	NM_001650.7	ENSP00000372654.4		P55087-1

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26477

AN:

151474

Hom.:

2575

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.367

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.194

GnomAD4 exome

AF:

0.213

AC:

98650

AN:

462494

Hom.:

11239

AF XY:

0.219

AC XY:

53465

AN XY:

244314

show subpopulations

African (AFR)

AF:

0.104

AC:

1316

AN:

12598

American (AMR)

AF:

0.133

AC:

2529

AN:

18950

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

3690

AN:

15050

East Asian (EAS)

AF:

0.368

AC:

11363

AN:

30884

South Asian (SAS)

AF:

0.307

AC:

13886

AN:

45236

European-Finnish (FIN)

AF:

0.174

AC:

5466

AN:

31454

Middle Eastern (MID)

AF:

0.202

AC:

449

AN:

2226

European-Non Finnish (NFE)

AF:

0.195

AC:

54679

AN:

279840

Other (OTH)

AF:

0.201

AC:

5272

AN:

26256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

3564

7128

10692

14256

17820

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.175

AC:

26459

AN:

151592

Hom.:

2569

Cov.:

AF XY:

0.177

AC XY:

13106

AN XY:

74070

show subpopulations

African (AFR)

AF:

0.102

AC:

4197

AN:

41234

American (AMR)

AF:

0.141

AC:

2143

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

883

AN:

3464

East Asian (EAS)

AF:

0.366

AC:

1890

AN:

5158

South Asian (SAS)

AF:

0.300

AC:

1440

AN:

4800

European-Finnish (FIN)

AF:

0.164

AC:

1726

AN:

10516

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.199

AC:

13538

AN:

67950

Other (OTH)

AF:

0.191

AC:

399

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1148

2296

3443

4591

5739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.185

Hom.:

3397

Bravo

AF:

0.164

Asia WGS

AF:

0.292

AC:

1013

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

0.63

PromoterAI

-0.037

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs162007

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over