Genetic Variant AQP5:c.363+20_363+21dupGG (chr12-49962391-T-TGG) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001651.4(AQP5):c.363+20_363+21dupGG variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 7 hom., cov: 0)

Exomes 𝑓: 0.00014 ( 0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 12-49962391-T-TGG is Benign according to our data. Variant chr12-49962391-T-TGG is described in ClinVar as Benign. ClinVar VariationId is 2903493.Status of the report is criteria_provided_single_submitter, 1 stars.

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+20_363+21dupGG	intron	N/A	NP_001642.1	P55064
AQP5-AS1	NR_110589.1		n.258+274_258+275dupCC	intron	N/A
AQP5-AS1	NR_110590.1		n.256+274_256+275dupCC	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AQP5	ENST00000293599.7	TSL:1 MANE Select	c.363+11_363+12insGG	intron	N/A	ENSP00000293599.5	P55064
AQP5	ENST00000857226.1		c.363+11_363+12insGG	intron	N/A	ENSP00000527285.1
AQP5-AS1	ENST00000550214.2	TSL:2	n.286+275_286+276insCC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00362

AC:

543

AN:

149822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00241

Gnomad SAS

AF:

0.000419

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000964

GnomAD4 exome

AF:

0.000143

AC:

198

AN:

1386768

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

685738

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00539

AC:

159

AN:

29500

American (AMR)

AF:

0.0000534

AC:

AN:

37488

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23016

East Asian (EAS)

AF:

0.000660

AC:

AN:

36346

South Asian (SAS)

AF:

0.0000130

AC:

AN:

77178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3852

European-Non Finnish (NFE)

AF:

9.22e-7

AC:

AN:

1084492

Other (OTH)

AF:

0.000193

AC:

AN:

57074

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.312

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00363

AC:

545

AN:

149934

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

246

AN XY:

73252

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0128

AC:

509

AN:

39734

American (AMR)

AF:

0.00124

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00242

AC:

AN:

4964

South Asian (SAS)

AF:

0.000419

AC:

AN:

4772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67880

Other (OTH)

AF:

0.000954

AC:

AN:

2096

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.373

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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.:

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

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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12-49962391-TGGGG-TGGGGGG

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