Genetic Variant ENST00000578701.5:n.54+368C>T (chr18-26865728-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000578701.5(AQP4-AS1):n.54+368C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,612,618 control chromosomes in the GnomAD database, including 33,551 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 0.17 ( 2562 hom., cov: 33)

Exomes 𝑓: 0.20 ( 30989 hom. )

Consequence

AQP4-AS1
ENST00000578701.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.391

Variant links:

Genes affected

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

AQP4-AS1 links:

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP4	NM_001650.7 link	c.-39G>A		upstream_gene_variant		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.-39G>A		upstream_gene_variant		1	NM_001650.7	ENSP00000372654.4		P55087-1

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26476

AN:

152028

Hom.:

2568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.363

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.190

GnomAD3 exomes

AF:

0.204

AC:

51209

AN:

251046

Hom.:

5919

AF XY:

0.212

AC XY:

28775

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.100

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.239

Gnomad EAS exome

AF:

0.368

Gnomad SAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.197

Gnomad OTH exome

AF:

0.205

GnomAD4 exome

AF:

0.201

AC:

293643

AN:

1460472

Hom.:

30989

Cov.:

AF XY:

0.204

AC XY:

148466

AN XY:

726634

show subpopulations

Gnomad4 AFR exome

AF:

0.0981

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.242

Gnomad4 EAS exome

AF:

0.364

Gnomad4 SAS exome

AF:

0.295

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.174

AC:

26458

AN:

152146

Hom.:

2562

Cov.:

AF XY:

0.176

AC XY:

13116

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.142

Gnomad4 ASJ

AF:

0.255

Gnomad4 EAS

AF:

0.363

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.163

Gnomad4 NFE

AF:

0.199

Gnomad4 OTH

AF:

0.188

Alfa

AF:

0.167

Hom.:

1018

Bravo

AF:

0.165

Asia WGS

AF:

0.291

AC:

1011

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.7

DANN

Benign

0.89

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

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