15-58179780-G-C

Variant names:

• chr15-58179780-G-C
• rs16939881
• NM_020980.5:c.713+435G>C

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+435G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 152,192 control chromosomes in the GnomAD database, including 267 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 0.025 (267 hom., cov: 32)
• Consequence: AQP9 NM_020980.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP9	NM_020980.5	c.713+435G>C		intron_variant	Intron 5 of 5	ENST00000219919.9	NP_066190.2
AQP9	NM_001320636.1	c.518+435G>C		intron_variant	Intron 5 of 5		NP_001307565.1
AQP9	NM_001320635.2	c.496-4181G>C		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.713+435G>C		intron_variant	Intron 5 of 5	1	NM_020980.5	ENSP00000219919.4

Frequencies

GnomAD3 genomes AF: 0.0248 AC: 3768 AN: 152074 Hom.: 263 Cov.: 32

Gnomad AFR AF: 0.00447

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.0799

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.0701

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00178

Gnomad OTH AF: 0.0284

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

GnomAD4 genome AF: 0.0249 AC: 3783 AN: 152192 Hom.: 267 Cov.: 32 AF XY: 0.0307 AC XY: 2282 AN XY: 74410

African (AFR) AF: 0.00445 AC: 185 AN: 41536

American (AMR) AF: 0.146 AC: 2228 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3464

East Asian (EAS) AF: 0.0802 AC: 415 AN: 5172

South Asian (SAS) AF: 0.00642 AC: 31 AN: 4828

European-Finnish (FIN) AF: 0.0701 AC: 742 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00178 AC: 121 AN: 68026

Other (OTH) AF: 0.0281 AC: 59 AN: 2098

Alfa AF: 0.00339 Hom.: 0

Bravo AF: 0.0330

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.27
DANN	Benign	0.42
PhyloP100		-0.86
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: rs16939881; hg19: chr15-58471979;