rs2899619

Variant summary

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

The NM_020980.5(AQP9):​c.713+662C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,936 control chromosomes in the GnomAD database, including 18,198 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 0.48 ( 18198 hom., cov: 32)

Consequence

AQP9
NM_020980.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20
Variant links:
Genes affected
AQP9 (HGNC:643): (aquaporin 9) The aquaporins are a family of water-selective membrane channels. This gene encodes a member of a subset of aquaporins called the aquaglyceroporins. This protein allows passage of a broad range of noncharged solutes and also stimulates urea transport and osmotic water permeability. This protein may also facilitate the uptake of glycerol in hepatic tissue . The encoded protein may also play a role in specialized leukocyte functions such as immunological response and bactericidal activity. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
ALDH1A2 (HGNC:15472): (aldehyde dehydrogenase 1 family member A2) This protein belongs to the aldehyde dehydrogenase family of proteins. The product of this gene is an enzyme that catalyzes the synthesis of retinoic acid (RA) from retinaldehyde. Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that functions in developing and adult tissues. The studies of a similar mouse gene suggest that this enzyme and the cytochrome CYP26A1, concurrently establish local embryonic retinoic acid levels which facilitate posterior organ development and prevent spina bifida. Four transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2011]

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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=-0.81).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AQP9NM_020980.5 linkuse as main transcriptc.713+662C>T intron_variant ENST00000219919.9 NP_066190.2 O43315
AQP9NM_001320636.1 linkuse as main transcriptc.518+662C>T intron_variant NP_001307565.1 H0YK62
AQP9NM_001320635.2 linkuse as main transcriptc.496-3954C>T intron_variant NP_001307564.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AQP9ENST00000219919.9 linkuse as main transcriptc.713+662C>T intron_variant 1 NM_020980.5 ENSP00000219919.4 O43315

Frequencies

GnomAD3 genomes
AF:
0.480
AC:
72859
AN:
151818
Hom.:
18182
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.353
Gnomad AMI
AF:
0.423
Gnomad AMR
AF:
0.604
Gnomad ASJ
AF:
0.623
Gnomad EAS
AF:
0.579
Gnomad SAS
AF:
0.553
Gnomad FIN
AF:
0.479
Gnomad MID
AF:
0.500
Gnomad NFE
AF:
0.509
Gnomad OTH
AF:
0.507
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.480
AC:
72907
AN:
151936
Hom.:
18198
Cov.:
32
AF XY:
0.484
AC XY:
35910
AN XY:
74234
show subpopulations
Gnomad4 AFR
AF:
0.353
Gnomad4 AMR
AF:
0.605
Gnomad4 ASJ
AF:
0.623
Gnomad4 EAS
AF:
0.578
Gnomad4 SAS
AF:
0.554
Gnomad4 FIN
AF:
0.479
Gnomad4 NFE
AF:
0.509
Gnomad4 OTH
AF:
0.507
Alfa
AF:
0.500
Hom.:
4554
Bravo
AF:
0.483
Asia WGS
AF:
0.547
AC:
1901
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.72
DANN
Benign
0.64

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.

Other links and lift over

dbSNP: rs2899619; hg19: chr15-58472206; API