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GeneBe

16-25217245-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001169.3(AQP8):c.60G>A(p.Pro20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,614,206 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0088 ( 20 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 17 hom. )

Consequence

AQP8
NM_001169.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.336
Variant links:
Genes affected
AQP8 (HGNC:642): (aquaporin 8) Aquaporin 8 (AQP8) is a water channel protein. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein (MIP or AQP0). Aquaporin 8 mRNA is found in pancreas and colon but not other tissues. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-25217245-G-A is Benign according to our data. Variant chr16-25217245-G-A is described in ClinVar as [Benign]. Clinvar id is 778581.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.336 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00879 (1339/152324) while in subpopulation AFR AF= 0.0271 (1125/41564). AF 95% confidence interval is 0.0258. There are 20 homozygotes in gnomad4. There are 641 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 20 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AQP8NM_001169.3 linkuse as main transcriptc.60G>A p.Pro20= synonymous_variant 2/6 ENST00000219660.6
AQP8XM_011545822.3 linkuse as main transcriptc.63G>A p.Pro21= synonymous_variant 2/6
AQP8XM_011545823.3 linkuse as main transcriptc.63G>A p.Pro21= synonymous_variant 2/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AQP8ENST00000219660.6 linkuse as main transcriptc.60G>A p.Pro20= synonymous_variant 2/61 NM_001169.3 P4
AQP8ENST00000566125.5 linkuse as main transcriptc.42G>A p.Pro14= synonymous_variant 2/61 A1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00876
AC:
1334
AN:
152206
Hom.:
20
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0270
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00740
Gnomad ASJ
AF:
0.00519
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.000794
Gnomad OTH
AF:
0.0115
GnomAD3 exomes
AF:
0.00309
AC:
777
AN:
251388
Hom.:
5
AF XY:
0.00265
AC XY:
360
AN XY:
135852
show subpopulations
Gnomad AFR exome
AF:
0.0290
Gnomad AMR exome
AF:
0.00358
Gnomad ASJ exome
AF:
0.00596
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000853
Gnomad OTH exome
AF:
0.00342
GnomAD4 exome
AF:
0.00159
AC:
2331
AN:
1461882
Hom.:
17
Cov.:
31
AF XY:
0.00152
AC XY:
1107
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0318
Gnomad4 AMR exome
AF:
0.00389
Gnomad4 ASJ exome
AF:
0.00582
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.000131
Gnomad4 NFE exome
AF:
0.000588
Gnomad4 OTH exome
AF:
0.00373
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00879
AC:
1339
AN:
152324
Hom.:
20
Cov.:
32
AF XY:
0.00860
AC XY:
641
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0271
Gnomad4 AMR
AF:
0.00739
Gnomad4 ASJ
AF:
0.00519
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000794
Gnomad4 OTH
AF:
0.0114
Alfa
AF:
0.00496
Hom.:
1
Bravo
AF:
0.0104
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.00109
EpiControl
AF:
0.00113

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 08, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
1.3
Dann
Benign
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs139992979; hg19: chr16-25228566; API