Genetic Variant AQP5:c.363+21delG (chr12-49962391-TG-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001651.4(AQP5):c.363+21delG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.21 ( 3508 hom., cov: 0)

Exomes 𝑓: 0.20 ( 27433 hom. )

Consequence

AQP5
NM_001651.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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 -10 ACMG points.

BP6

Variant 12-49962391-TG-T is Benign according to our data. Variant chr12-49962391-TG-T is described in ClinVar as Benign. ClinVar VariationId is 1578048.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 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+21delG	intron	N/A	NP_001642.1	P55064
AQP5-AS1	NR_110589.1		n.258+275delC	intron	N/A
AQP5-AS1	NR_110590.1		n.256+275delC	intron	N/A

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31280

AN:

149732

Hom.:

3512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.326

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.298

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.237

GnomAD2 exomes

AF:

0.189

AC:

32112

AN:

170032

AF XY:

0.197

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.354

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.198

AC:

274746

AN:

1385502

Hom.:

27433

Cov.:

AF XY:

0.202

AC XY:

138245

AN XY:

684994

show subpopulations

African (AFR)

AF:

0.231

AC:

6823

AN:

29582

American (AMR)

AF:

0.117

AC:

4380

AN:

37386

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

5291

AN:

22950

East Asian (EAS)

AF:

0.361

AC:

13104

AN:

36298

South Asian (SAS)

AF:

0.311

AC:

23919

AN:

76950

European-Finnish (FIN)

AF:

0.160

AC:

6060

AN:

37758

Middle Eastern (MID)

AF:

0.312

AC:

1202

AN:

3852

European-Non Finnish (NFE)

AF:

0.186

AC:

201353

AN:

1083692

Other (OTH)

AF:

0.221

AC:

12614

AN:

57034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

11684

23368

35051

46735

58419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7442

14884

22326

29768

37210

<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:

0.209

AC:

31277

AN:

149848

Hom.:

3508

Cov.:

AF XY:

0.210

AC XY:

15359

AN XY:

73214

show subpopulations

African (AFR)

AF:

0.231

AC:

9190

AN:

39770

American (AMR)

AF:

0.153

AC:

2333

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

850

AN:

3464

East Asian (EAS)

AF:

0.366

AC:

1813

AN:

4952

South Asian (SAS)

AF:

0.325

AC:

1548

AN:

4756

European-Finnish (FIN)

AF:

0.179

AC:

1885

AN:

10546

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.190

AC:

12914

AN:

67816

Other (OTH)

AF:

0.234

AC:

491

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1035

2070

3105

4140

5175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.195

Hom.:

366

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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12-49962391-TGGGG-TGGG

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