Variant 16-25217245-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001169.3(AQP8):c.60G>A(p.Pro20Pro) 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

Clinical Significance

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

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]

AQP8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.336 with no splicing effect.

BS1

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

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP8	NM_001169.3 linkuse as main transcript	c.60G>A	p.Pro20Pro	synonymous_variant	2/6	ENST00000219660.6	NP_001160.2	O94778
AQP8	XM_011545822.3 linkuse as main transcript	c.63G>A	p.Pro21Pro	synonymous_variant	2/6		XP_011544124.1
AQP8	XM_011545823.3 linkuse as main transcript	c.63G>A	p.Pro21Pro	synonymous_variant	2/4		XP_011544125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP8	ENST00000219660.6 linkuse as main transcript	c.60G>A	p.Pro20Pro	synonymous_variant	2/6	1	NM_001169.3	ENSP00000219660.5		O94778
AQP8	ENST00000566125.5 linkuse as main transcript	c.42G>A	p.Pro14Pro	synonymous_variant	2/6	1		ENSP00000454457.1		A0A0C4DGL6

Frequencies

GnomAD3 genomes

AF:

0.00876

AC:

1334

AN:

152206

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00879

AC:

1339

AN:

152324

Hom.:

Cov.:

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.:

Bravo

AF:

0.0104

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00113

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	Jun 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.

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