dbSNP rs335929: AQP4:c.*588T>G (chr18-26855623-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001650.7(AQP4):c.*588T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 153,808 control chromosomes in the GnomAD database, including 2,423 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 0.16 ( 2399 hom., cov: 33)

Exomes 𝑓: 0.18 ( 24 hom. )

Consequence

AQP4
NM_001650.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.318

Publications

22 publications found

Variant links:

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 links:

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

AQP4-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP4	NM_001650.7 link	c.*588T>G		3_prime_UTR_variant	Exon 5 of 5	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.*588T>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_001650.7	ENSP00000372654.4		P55087-1

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23723

AN:

152078

Hom.:

2407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0415

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.393

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.169

GnomAD4 exome

AF:

0.176

AC:

283

AN:

1612

Hom.:

Cov.:

AF XY:

0.172

AC XY:

150

AN XY:

874

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.103

AC:

AN:

214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.226

AC:

AN:

European-Finnish (FIN)

AF:

0.186

AC:

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.187

AC:

161

AN:

860

Other (OTH)

AF:

0.111

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.156

AC:

23710

AN:

152196

Hom.:

2399

Cov.:

AF XY:

0.159

AC XY:

11865

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0416

AC:

1730

AN:

41562

American (AMR)

AF:

0.132

AC:

2025

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

886

AN:

3466

East Asian (EAS)

AF:

0.393

AC:

2032

AN:

5166

South Asian (SAS)

AF:

0.331

AC:

1597

AN:

4820

European-Finnish (FIN)

AF:

0.156

AC:

1655

AN:

10590

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.194

AC:

13190

AN:

67982

Other (OTH)

AF:

0.167

AC:

354

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

973

1947

2920

3894

4867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.184

Hom.:

6242

Bravo

AF:

0.143

Asia WGS

AF:

0.308

AC:

1070

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.7

(source)

DANN

Benign

0.48

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs335929

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