dbSNP rs72557968: AQP4:p.Gln122Gln (chr18-26862263-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001650.7(AQP4):c.366G>A(p.Gln122Gln) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.15

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AQP4	NM_001650.7 link	c.366G>A	p.Gln122Gln	synonymous_variant	Exon 2 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.366G>A	p.Gln122Gln	synonymous_variant	Exon 2 of 5	1	NM_001650.7	ENSP00000372654.4		P55087-1

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2736

AN:

152168

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0263

AC:

6620

AN:

251376

AF XY:

0.0310

show subpopulations

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 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.:

AF XY:

0.0246

AC XY:

17875

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00938

AC:

314

AN:

33480

American (AMR)

AF:

0.00823

AC:

368

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0222

AC:

579

AN:

26136

East Asian (EAS)

AF:

0.00169

AC:

AN:

39700

South Asian (SAS)

AF:

0.0906

AC:

7817

AN:

86258

European-Finnish (FIN)

AF:

0.0350

AC:

1871

AN:

53404

Middle Eastern (MID)

AF:

0.0352

AC:

203

AN:

5768

European-Non Finnish (NFE)

AF:

0.0182

AC:

20238

AN:

1112012

Other (OTH)

AF:

0.0192

AC:

1158

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

2078

4157

6235

8314

10392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

854

1708

2562

3416

4270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0179

AC:

2733

AN:

152286

Hom.:

Cov.:

AF XY:

0.0205

AC XY:

1523

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00989

AC:

411

AN:

41562

American (AMR)

AF:

0.0110

AC:

169

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

AN:

3470

East Asian (EAS)

AF:

0.00387

AC:

AN:

5174

South Asian (SAS)

AF:

0.0935

AC:

451

AN:

4826

European-Finnish (FIN)

AF:

0.0358

AC:

380

AN:

10602

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0175

AC:

1193

AN:

68024

Other (OTH)

AF:

0.0128

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

129

258

386

515

644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0176

Hom.:

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

(source)

DANN

Benign

0.87

PhyloP100

3.1

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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