rs2287800

chr16-25217193-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001169.3(AQP8):c.13-5G>A variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.1893
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQP8	NM_001169.3	c.13-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000219660.6
AQP8	XM_011545822.3	c.13-2G>A		splice_acceptor_variant
AQP8	XM_011545823.3	c.13-2G>A		splice_acceptor_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP8	ENST00000219660.6	c.13-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001169.3	P4
AQP8	ENST00000566125.5	c.-6-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 269 AN: 152112 Hom.: 4 Cov.: 32

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

GnomAD3 exomes AF: 0.00225 AC: 564 AN: 250994 Hom.: 2 AF XY: 0.00246 AC XY: 334 AN XY: 135690

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 SAS exome AF: 0.00131

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.: 9 Cov.: 31 AF XY: 0.00113 AC XY: 820 AN XY: 727136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00130

Gnomad4 ASJ exome AF: 0.00115

Gnomad4 EAS exome AF: 0.00960

Gnomad4 SAS exome AF: 0.00140

Gnomad4 FIN exome AF: 0.0116

Gnomad4 NFE exome AF: 0.000223

Gnomad4 OTH exome AF: 0.00132

GnomAD4 genome AF: 0.00177 AC: 269 AN: 152230 Hom.: 4 Cov.: 32 AF XY: 0.00232 AC XY: 173 AN XY: 74424

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0110

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0145

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000792 Hom.: 0

Bravo AF: 0.000533

Asia WGS AF: 0.00664 AC: 23 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	17
Dann	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs2287800; hg19: chr16-25228514; COSMIC: COSV54845505;