Variant 18-26862428-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001650.7(AQP4):c.201G>T(p.Pro67=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,614,072 control chromosomes in the GnomAD database, including 11,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.087 ( 810 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10275 hom. )

Consequence

AQP4
NM_001650.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.47

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 18-26862428-C-A is Benign according to our data. Variant chr18-26862428-C-A is described in ClinVar as [Benign]. Clinvar id is 3060164.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.47 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 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.201G>T	p.Pro67=	synonymous_variant	2/5	ENST00000383168.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP4	ENST00000383168.9 linkuse as main transcript	c.201G>T	p.Pro67=	synonymous_variant	2/5	1	NM_001650.7	P1	P55087-1

Frequencies

GnomAD3 genomes

AF:

0.0874

AC:

13286

AN:

152070

Hom.:

810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.0943

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0253

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.105

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.0941

GnomAD3 exomes

AF:

0.0896

AC:

22519

AN:

251424

Hom.:

1317

AF XY:

0.0899

AC XY:

12216

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0208

Gnomad AMR exome

AF:

0.0673

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0279

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.112

AC:

163222

AN:

1461884

Hom.:

10275

Cov.:

AF XY:

0.110

AC XY:

79750

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0177

Gnomad4 AMR exome

AF:

0.0682

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0296

Gnomad4 FIN exome

AF:

0.146

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.106

GnomAD4 genome

AF:

0.0873

AC:

13284

AN:

152188

Hom.:

810

Cov.:

AF XY:

0.0873

AC XY:

6490

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0223

Gnomad4 AMR

AF:

0.0942

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0253

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.0931

Alfa

AF:

0.105

Hom.:

436

Bravo

AF:

0.0802

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.119

EpiControl

AF:

0.119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AQP4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.036

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over