Genetic Variant AQP5:c.363+6T>G (chr12-49962386-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_001651.4(AQP5):c.363+6T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,391,158 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0017 ( 3 hom. )

Consequence

AQP5
NM_001651.4 splice_region, intron

Scores

Splicing: ADA: 0.3655

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.29

Publications

0 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 12-49962386-T-G is Benign according to our data. Variant chr12-49962386-T-G is described in ClinVar as Benign. ClinVar VariationId is 731677.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00498 (98/19666) while in subpopulation NFE AF = 0.0207 (89/4298). AF 95% confidence interval is 0.0172. There are 0 homozygotes in GnomAd4. There are 37 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.

BS2

High AC in GnomAd4 at 98 AD gene.

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+6T>G	splice_region intron	N/A	NP_001642.1	P55064
AQP5-AS1	NR_110589.1		n.258+281A>C	intron	N/A
AQP5-AS1	NR_110590.1		n.256+281A>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AQP5	ENST00000293599.7	TSL:1 MANE Select	c.363+6T>G	splice_region intron	N/A	ENSP00000293599.5	P55064
AQP5	ENST00000857226.1		c.363+6T>G	splice_region intron	N/A	ENSP00000527285.1
AQP5-AS1	ENST00000550214.2	TSL:2	n.286+281A>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00499

AC:

AN:

19654

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0207

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00803

AC:

176

AN:

21916

AF XY:

0.00771

show subpopulations

Gnomad AFR exome

AF:

0.000830

Gnomad AMR exome

AF:

0.00100

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00268

Gnomad NFE exome

AF:

0.0143

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00170

AC:

2328

AN:

1371492

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1083

AN XY:

680780

show subpopulations

African (AFR)

AF:

0.000272

AC:

AN:

25776

American (AMR)

AF:

0.0000495

AC:

AN:

40376

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22378

East Asian (EAS)

AF:

0.0000303

AC:

AN:

33002

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80548

European-Finnish (FIN)

AF:

0.000150

AC:

AN:

39948

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3754

European-Non Finnish (NFE)

AF:

0.00211

AC:

2264

AN:

1070816

Other (OTH)

AF:

0.000856

AC:

AN:

54894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

127

255

382

510

637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<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:

0.00498

AC:

AN:

19666

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

AN XY:

9446

show subpopulations

African (AFR)

AF:

0.000506

AC:

AN:

11854

American (AMR)

AF:

0.00209

AC:

AN:

1436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

320

East Asian (EAS)

AF:

0.00

AC:

AN:

570

South Asian (SAS)

AF:

0.00

AC:

AN:

304

European-Finnish (FIN)

AF:

0.00

AC:

AN:

620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0207

AC:

AN:

4298

Other (OTH)

AF:

0.00

AC:

AN:

196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

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

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

3.3

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.37

dbscSNV1_RF

Benign

0.43

SpliceAI score (max)

0.030

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.

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