Variant chr18-26861251-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001650.7(AQP4):c.492G>A(p.Leu164=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 1,614,006 control chromosomes in the GnomAD database, including 799 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 0.025 ( 69 hom., cov: 33)

Exomes 𝑓: 0.023 ( 730 hom. )

Consequence

AQP4
NM_001650.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02

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 made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP7

Synonymous conserved (PhyloP=2.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQP4	NM_001650.7 linkuse as main transcript	c.492G>A	p.Leu164=	synonymous_variant	3/5	ENST00000383168.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP4	ENST00000383168.9 linkuse as main transcript	c.492G>A	p.Leu164=	synonymous_variant	3/5	1	NM_001650.7	P1	P55087-1

Frequencies

GnomAD3 genomes

AF:

0.0247

AC:

3753

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0330

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.0986

Gnomad FIN

AF:

0.0360

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0176

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0286

AC:

7180

AN:

251384

Hom.:

215

AF XY:

0.0329

AC XY:

4468

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0348

Gnomad AMR exome

AF:

0.00899

Gnomad ASJ exome

AF:

0.0242

Gnomad EAS exome

AF:

0.00234

Gnomad SAS exome

AF:

0.0989

Gnomad FIN exome

AF:

0.0365

Gnomad NFE exome

AF:

0.0181

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0232

AC:

33931

AN:

1461706

Hom.:

730

Cov.:

AF XY:

0.0255

AC XY:

18517

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.0344

Gnomad4 AMR exome

AF:

0.00903

Gnomad4 ASJ exome

AF:

0.0222

Gnomad4 EAS exome

AF:

0.00169

Gnomad4 SAS exome

AF:

0.0946

Gnomad4 FIN exome

AF:

0.0350

Gnomad4 NFE exome

AF:

0.0182

Gnomad4 OTH exome

AF:

0.0208

GnomAD4 genome

AF:

0.0246

AC:

3753

AN:

152300

Hom.:

Cov.:

AF XY:

0.0268

AC XY:

1993

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0330

Gnomad4 AMR

AF:

0.0124

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.00366

Gnomad4 SAS

AF:

0.0983

Gnomad4 FIN

AF:

0.0360

Gnomad4 NFE

AF:

0.0176

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0201

Hom.:

Bravo

AF:

0.0216

Asia WGS

AF:

0.0450

AC:

157

AN:

3478

EpiCase

AF:

0.0186

EpiControl

AF:

0.0175

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over