rs2899619

Positions:

• chr15-58180007-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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]

ALDH1A2 (HGNC:):

ACMG classification

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
AQP9	NM_020980.5	c.713+662C>T		intron_variant		ENST00000219919.9	NP_066190.2
AQP9	NM_001320636.1	c.518+662C>T		intron_variant			NP_001307565.1
AQP9	NM_001320635.2	c.496-3954C>T		intron_variant			NP_001307564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP9	ENST00000219919.9	c.713+662C>T		intron_variant		1	NM_020980.5	ENSP00000219919.4

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72859 AN: 151818 Hom.: 18182 Cov.: 32

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

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

Other links and lift over

dbSNP: rs2899619; hg19: chr15-58472206;