dbSNP rs2287800: AQP8:c.13-5G>A (chr16-25217193-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001169.3(AQP8):c.13-5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,613,882 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0018 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 9 hom. )

Consequence

AQP8
NM_001169.3 splice_region, intron

Scores

Splicing: ADA: 0.1893

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.13

Publications

4 publications found

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:

ENSG00000309232 (HGNC:):

ENSG00000309232 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AQP8	NM_001169.3 link	c.13-5G>A	splice_region_variant, intron_variant	Intron 1 of 5	ENST00000219660.6	NP_001160.2	O94778
AQP8	XM_011545822.3 link	c.13-2G>A	splice_acceptor_variant, intron_variant	Intron 1 of 5		XP_011544124.1
AQP8	XM_011545823.3 link	c.13-2G>A	splice_acceptor_variant, intron_variant	Intron 1 of 3		XP_011544125.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AQP8	ENST00000219660.6 link	c.13-5G>A	splice_region_variant, intron_variant	Intron 1 of 5	1	NM_001169.3	ENSP00000219660.5	O94778
AQP8	ENST00000566125.5 link	c.-6-5G>A	splice_region_variant, intron_variant	Intron 1 of 5	1		ENSP00000454457.1	A0A0C4DGL6
ENSG00000309232	ENST00000839745.1 link	n.149+5877C>T	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00177

AC:

269

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0145

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00225

AC:

564

AN:

250994

AF XY:

0.00246

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00653

Gnomad FIN exome

AF:

0.0111

Gnomad NFE exome

AF:

0.000705

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00105

AC:

1535

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

820

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00130

AC:

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

26126

East Asian (EAS)

AF:

0.00960

AC:

381

AN:

39696

South Asian (SAS)

AF:

0.00140

AC:

121

AN:

86246

European-Finnish (FIN)

AF:

0.0116

AC:

616

AN:

53288

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000223

AC:

248

AN:

1111992

Other (OTH)

AF:

0.00132

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

106

211

317

422

528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00177

AC:

269

AN:

152230

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

173

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41548

American (AMR)

AF:

0.000458

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3468

East Asian (EAS)

AF:

0.0110

AC:

AN:

5182

South Asian (SAS)

AF:

0.00145

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0145

AC:

154

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68018

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000792

Hom.:

Bravo

AF:

0.000533

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

-2.1

PromoterAI

-0.015

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.19

dbscSNV1_RF

Benign

0.55

SpliceAI score (max)

0.84

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.84

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over