Genetic Variant AQP5:c.612+216C>A (chr12-49964391-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001651.4(AQP5):c.612+216C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,956 control chromosomes in the GnomAD database, including 5,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 5051 hom., cov: 31)

Consequence

AQP5
NM_001651.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.61

Publications

6 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:

LOC105369764 (HGNC:):

LOC105369764 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 12-49964391-C-A is Benign according to our data. Variant chr12-49964391-C-A is described in ClinVar as Benign. ClinVar VariationId is 1225148.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP5	NM_001651.4	MANE Select	c.612+216C>A		intron	N/A	NP_001642.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AQP5	ENST00000293599.7	TSL:1 MANE Select	c.612+216C>A	intron	N/A	ENSP00000293599.5
AQP5	ENST00000553132.1	TSL:2	n.601+216C>A	intron	N/A
AQP5-AS1	ENST00000750790.1		n.301+1292G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

33952

AN:

151836

Hom.:

5042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.433

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.0953

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.245

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.200

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

GnomAD4 genome

AF:

0.224

AC:

33999

AN:

151956

Hom.:

5051

Cov.:

AF XY:

0.220

AC XY:

16343

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.434

AC:

17938

AN:

41370

American (AMR)

AF:

0.157

AC:

2391

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

665

AN:

3472

East Asian (EAS)

AF:

0.183

AC:

946

AN:

5168

South Asian (SAS)

AF:

0.0944

AC:

454

AN:

4810

European-Finnish (FIN)

AF:

0.130

AC:

1375

AN:

10586

Middle Eastern (MID)

AF:

0.247

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.141

AC:

9595

AN:

67960

Other (OTH)

AF:

0.197

AC:

416

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1194

2389

3583

4778

5972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.187

Hom.:

3156

Bravo

AF:

0.236

Asia WGS

AF:

0.145

AC:

508

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.020

(source)

DANN

Benign

0.59

PhyloP100

-2.6

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over