rs1618930

chr15-58175767-A-Cchr15-58175767-A-Gchr15-58175767-A-T

Variant summary

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

The NM_020980.5(AQP9):c.495+731A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,146 control chromosomes in the GnomAD database, including 16,546 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 0.44 (16546 hom., cov: 33)
• Consequence: AQP9 NM_020980.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQP9	NM_020980.5	c.495+731A>C		intron_variant		ENST00000219919.9
AQP9	NM_001320635.2	c.495+731A>C		intron_variant
AQP9	NM_001320636.1	c.300+731A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP9	ENST00000219919.9	c.495+731A>C		intron_variant		1	NM_020980.5	P1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66992 AN: 152028 Hom.: 16535 Cov.: 33

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.479

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.441 AC: 67025 AN: 152146 Hom.: 16546 Cov.: 33 AF XY: 0.445 AC XY: 33097 AN XY: 74376

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.483

Alfa AF: 0.510 Hom.: 27298

Bravo AF: 0.439

Asia WGS AF: 0.542 AC: 1885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.2
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1618930; hg19: chr15-58467966;