12-49962391-TGGGG-TGG

Variant names:

• chr12-49962391-TGG-T
• rs3832811
• NM_001651.4:c.363+20_363+21delGG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001651.4(AQP5):​c.363+20_363+21delGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,535,648 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: AQP5 NM_001651.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227

Genes affected

AQP5 (HGNC:638): (aquaporin 5) Aquaporin 5 (AQP5) is a water channel protein. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein (MIP or AQP0). Aquaporin 5 plays a role in the generation of saliva, tears and pulmonary secretions. AQP0, AQP2, AQP5, and AQP6 are closely related and all map to 12q13. [provided by RefSeq, Jul 2008]

AQP5-AS1 (HGNC:55474): (AQP5 and AQP2 antisense RNA 2)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP5	NM_001651.4	c.363+20_363+21delGG		intron_variant	Intron 1 of 3	ENST00000293599.7	NP_001642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP5	ENST00000293599.7	c.363+12_363+13delGG		intron_variant	Intron 1 of 3	1	NM_001651.4	ENSP00000293599.5
AQP5-AS1	ENST00000550214.1	n.258+274_258+275delCC		intron_variant	Intron 1 of 1	2
AQP5-AS1	ENST00000550530.1	n.117+274_117+275delCC		intron_variant	Intron 1 of 2	3
AQP5-AS1	ENST00000552379.1	n.256+274_256+275delCC		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.000107 AC: 16 AN: 149910 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.000482

GnomAD3 exomes AF: 0.000665 AC: 113 AN: 170032 Hom.: 0 AF XY: 0.000687 AC XY: 65 AN XY: 94654

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000114

Gnomad ASJ exome AF: 0.000633

Gnomad EAS exome AF: 0.00164

Gnomad SAS exome AF: 0.00165

Gnomad FIN exome AF: 0.000109

Gnomad NFE exome AF: 0.000538

Gnomad OTH exome AF: 0.000707

GnomAD4 exome AF: 0.000206 AC: 286 AN: 1385626 Hom.: 1 AF XY: 0.000229 AC XY: 157 AN XY: 685108

Gnomad4 AFR exome AF: 0.000404

Gnomad4 AMR exome AF: 0.000160

Gnomad4 ASJ exome AF: 0.000261

Gnomad4 EAS exome AF: 0.000524

Gnomad4 SAS exome AF: 0.000637

Gnomad4 FIN exome AF: 0.0000530

Gnomad4 NFE exome AF: 0.000160

Gnomad4 OTH exome AF: 0.000245

GnomAD4 genome AF: 0.000107 AC: 16 AN: 150022 Hom.: 0 Cov.: 0 AF XY: 0.0000819 AC XY: 6 AN XY: 73296

Gnomad4 AFR AF: 0.000151

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000737

Gnomad4 OTH AF: 0.000477

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3832811; hg19: chr12-50356174;