Variant 18-26856364-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001650.7(AQP4):c.819A>G(p.Thr273=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,614,262 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0052 ( 33 hom. )

Consequence

AQP4
NM_001650.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.69

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 made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 18-26856364-T-C is Benign according to our data. Variant chr18-26856364-T-C is described in ClinVar as [Benign]. Clinvar id is 790431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.69 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP4	NM_001650.7 linkuse as main transcript	c.819A>G	p.Thr273=	synonymous_variant	5/5	ENST00000383168.9	NP_001641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP4	ENST00000383168.9 linkuse as main transcript	c.819A>G	p.Thr273=	synonymous_variant	5/5	1	NM_001650.7	ENSP00000372654	P1	P55087-1

Frequencies

GnomAD3 genomes

AF:

0.00339

AC:

516

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00848

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00529

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00333

AC:

837

AN:

251486

Hom.:

AF XY:

0.00380

AC XY:

516

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00901

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.00410

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00519

AC:

7594

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00535

AC XY:

3888

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00885

Gnomad4 FIN exome

AF:

0.000693

Gnomad4 NFE exome

AF:

0.00576

Gnomad4 OTH exome

AF:

0.00429

GnomAD4 genome

AF:

0.00338

AC:

515

AN:

152368

Hom.:

Cov.:

AF XY:

0.00309

AC XY:

230

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00828

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00529

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00316

Hom.:

Bravo

AF:

0.00306

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.093

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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