NM_020980.5:c.713+662C>T

Variant names:

• chr15-58180007-C-T
• rs2899619
• NM_020980.5:c.713+662C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020980.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP9	NM_020980.5	MANE Select	c.713+662C>T		intron	N/A	NP_066190.2
	AQP9	NM_001320636.1		c.518+662C>T		intron	N/A	NP_001307565.1
	AQP9	NM_001320635.2		c.496-3954C>T		intron	N/A	NP_001307564.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP9	ENST00000219919.9	TSL:1 MANE Select	c.713+662C>T		intron	N/A	ENSP00000219919.4
	ALDH1A2	ENST00000558231.5	TSL:2	c.30+99167G>A		intron	N/A	ENSP00000453600.1
	AQP9	ENST00000558772.5	TSL:2	c.518+662C>T		intron	N/A	ENSP00000452673.1

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

African (AFR) AF: 0.353 AC: 14629 AN: 41446

American (AMR) AF: 0.605 AC: 9236 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2164 AN: 3472

East Asian (EAS) AF: 0.578 AC: 2976 AN: 5148

South Asian (SAS) AF: 0.554 AC: 2665 AN: 4812

European-Finnish (FIN) AF: 0.479 AC: 5048 AN: 10528

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34587 AN: 67944

Other (OTH) AF: 0.507 AC: 1071 AN: 2114

Alfa AF: 0.498 Hom.: 4617

Bravo AF: 0.483

Asia WGS AF: 0.547 AC: 1901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.72
DANN	Benign	0.64
PhyloP100		-1.2
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: rs2899619; hg19: chr15-58472206;