Genetic Variant AQP5:c.363+19_363+21delGGG (chr12-49962391-TGGG-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001651.4(AQP5):c.363+19_363+21delGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 1,537,074 control chromosomes in the GnomAD database, including 466,606 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38744 hom., cov: 0)

Exomes 𝑓: 0.78 ( 427862 hom. )

Consequence

AQP5
NM_001651.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.227

Variant links:

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 links:

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

AQP5-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 12-49962391-TGGG-T is Benign according to our data. Variant chr12-49962391-TGGG-T is described in ClinVar as [Benign]. Clinvar id is 1283355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP5	NM_001651.4 link	c.363+19_363+21delGGG		intron_variant	Intron 1 of 3	ENST00000293599.7	NP_001642.1	P55064

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AQP5	ENST00000293599.7 link	c.363+12_363+14delGGG	intron_variant	Intron 1 of 3	1	NM_001651.4	ENSP00000293599.5	P55064
AQP5-AS1	ENST00000550214.1 link	n.258+273_258+275delCCC	intron_variant	Intron 1 of 1	2
AQP5-AS1	ENST00000550530.1 link	n.117+273_117+275delCCC	intron_variant	Intron 1 of 2	3
AQP5-AS1	ENST00000552379.1 link	n.256+273_256+275delCCC	intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.707

AC:

105938

AN:

149896

Hom.:

38704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.511

Gnomad AMI

AF:

0.798

Gnomad AMR

AF:

0.800

Gnomad ASJ

AF:

0.718

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.817

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.802

Gnomad OTH

AF:

0.708

GnomAD2 exomes

AF:

0.772

AC:

131206

AN:

170032

AF XY:

0.768

show subpopulations

Gnomad AFR exome

AF:

0.553

Gnomad AMR exome

AF:

0.839

Gnomad ASJ exome

AF:

0.772

Gnomad EAS exome

AF:

0.537

Gnomad FIN exome

AF:

0.849

Gnomad NFE exome

AF:

0.823

Gnomad OTH exome

AF:

0.775

GnomAD4 exome

AF:

0.783

AC:

1086049

AN:

1387068

Hom.:

427862

AF XY:

0.780

AC XY:

534975

AN XY:

685860

show subpopulations

Gnomad4 AFR exome

AF:

0.515

AC:

15317

AN:

29766

Gnomad4 AMR exome

AF:

0.827

AC:

30990

AN:

37486

Gnomad4 ASJ exome

AF:

0.738

AC:

16981

AN:

22998

Gnomad4 EAS exome

AF:

0.530

AC:

19319

AN:

36442

Gnomad4 SAS exome

AF:

0.659

AC:

50848

AN:

77160

Gnomad4 FIN exome

AF:

0.832

AC:

31458

AN:

37810

Gnomad4 NFE exome

AF:

0.808

AC:

876040

AN:

1084432

Gnomad4 Remaining exome

AF:

0.745

AC:

42533

AN:

57120

Heterozygous variant carriers

13062

26125

39187

52250

65312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

20530

41060

61590

82120

102650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.707

AC:

106035

AN:

150006

Hom.:

38744

Cov.:

AF XY:

0.708

AC XY:

51868

AN XY:

73284

show subpopulations

Gnomad4 AFR

AF:

0.512

AC:

0.512082

AN:

0.512082

Gnomad4 AMR

AF:

0.800

AC:

0.799895

AN:

0.799895

Gnomad4 ASJ

AF:

0.718

AC:

0.718119

AN:

0.718119

Gnomad4 EAS

AF:

0.490

AC:

0.490133

AN:

0.490133

Gnomad4 SAS

AF:

0.639

AC:

0.638691

AN:

0.638691

Gnomad4 FIN

AF:

0.817

AC:

0.816597

AN:

0.816597

Gnomad4 NFE

AF:

0.802

AC:

0.802042

AN:

0.802042

Gnomad4 OTH

AF:

0.712

AC:

0.711832

AN:

0.711832

Heterozygous variant carriers

1332

2663

3995

5326

6658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

804

1608

2412

3216

4020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.764

Hom.:

366

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 18, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over