rs1711055

Variant names:

• chr15-58177385-C-G
• rs1711055
• NM_020980.5:c.496-1743C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020980.5(AQP9):​c.496-1743C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,250 control chromosomes in the GnomAD database, including 59,689 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 0.88 (59689 hom., cov: 33)
• Consequence: AQP9 NM_020980.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• diaphragmatic hernia 4, with cardiovascular defects

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP9	NM_020980.5	c.496-1743C>G		intron_variant	Intron 4 of 5	ENST00000219919.9	NP_066190.2
AQP9	NM_001320636.1	c.301-1743C>G		intron_variant	Intron 4 of 5		NP_001307565.1
AQP9	NM_001320635.2	c.495+2349C>G		intron_variant	Intron 4 of 4		NP_001307564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP9	ENST00000219919.9	c.496-1743C>G		intron_variant	Intron 4 of 5	1	NM_020980.5	ENSP00000219919.4

Frequencies

GnomAD3 genomes AF: 0.881 AC: 134058 AN: 152132 Hom.: 59651 Cov.: 33

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.896

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

GnomAD4 genome AF: 0.881 AC: 134154 AN: 152250 Hom.: 59689 Cov.: 33 AF XY: 0.880 AC XY: 65529 AN XY: 74456

African (AFR) AF: 0.751 AC: 31178 AN: 41508

American (AMR) AF: 0.910 AC: 13921 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3272 AN: 3472

East Asian (EAS) AF: 0.794 AC: 4120 AN: 5186

South Asian (SAS) AF: 0.862 AC: 4157 AN: 4824

European-Finnish (FIN) AF: 0.933 AC: 9903 AN: 10612

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.949 AC: 64564 AN: 68028

Other (OTH) AF: 0.897 AC: 1897 AN: 2114

Alfa AF: 0.914 Hom.: 7959

Bravo AF: 0.875

Asia WGS AF: 0.824 AC: 2865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.8
DANN	Benign	0.42
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1711055; hg19: chr15-58469584;