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

Publications

2 publications found

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:

Genome browser will be placed here

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001651.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AQP5	NM_001651.4	MANE Select	c.363+19_363+21delGGG	intron	N/A	NP_001642.1	P55064
AQP5-AS1	NR_110589.1		n.258+273_258+275delCCC	intron	N/A
AQP5-AS1	NR_110590.1		n.256+273_256+275delCCC	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AQP5	ENST00000293599.7	TSL:1 MANE Select	c.363+12_363+14delGGG	intron	N/A	ENSP00000293599.5	P55064
AQP5	ENST00000857226.1		c.363+12_363+14delGGG	intron	N/A	ENSP00000527285.1
AQP5-AS1	ENST00000550214.2	TSL:2	n.286+273_286+275delCCC	intron	N/A

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

African (AFR)

AF:

0.515

AC:

15317

AN:

29766

American (AMR)

AF:

0.827

AC:

30990

AN:

37486

Ashkenazi Jewish (ASJ)

AF:

0.738

AC:

16981

AN:

22998

East Asian (EAS)

AF:

0.530

AC:

19319

AN:

36442

South Asian (SAS)

AF:

0.659

AC:

50848

AN:

77160

European-Finnish (FIN)

AF:

0.832

AC:

31458

AN:

37810

Middle Eastern (MID)

AF:

0.665

AC:

2563

AN:

3854

European-Non Finnish (NFE)

AF:

0.808

AC:

876040

AN:

1084432

Other (OTH)

AF:

0.745

AC:

42533

AN:

57120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.540

Heterozygous variant carriers

13062

26125

39187

52250

65312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

African (AFR)

AF:

0.512

AC:

20387

AN:

39812

American (AMR)

AF:

0.800

AC:

12208

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.718

AC:

2489

AN:

3466

East Asian (EAS)

AF:

0.490

AC:

2434

AN:

4966

South Asian (SAS)

AF:

0.639

AC:

3044

AN:

4766

European-Finnish (FIN)

AF:

0.817

AC:

8620

AN:

10556

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.802

AC:

54441

AN:

67878

Other (OTH)

AF:

0.712

AC:

1492

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.552

Heterozygous variant carriers

1332

2663

3995

5326

6658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

12-49962391-TGGGG-TG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over