Genetic Variant AQP6:n.1357G>A (chr12-49972517-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000489786.5(AQP6):n.1357G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,254 control chromosomes in the GnomAD database, including 42,483 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.68 ( 42403 hom., cov: 31)

Exomes 𝑓: 0.88 ( 80 hom. )

Consequence

AQP6
ENST00000489786.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.120

Publications

14 publications found

Variant links:

Genes affected

AQP6 (HGNC:639): (aquaporin 6) The protein encoded by this gene is an aquaporin protein, which functions as a water channel in cells. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein (MIP or AQP0). This protein is specific for the kidney. This gene and related family members AQP0, AQP2, and AQP5 reside in a cluster on chromosome 12q13. [provided by RefSeq, Jul 2008]

AQP6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000489786.5. 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

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AQP6	ENST00000489786.5	TSL:1	n.1357G>A	non_coding_transcript_exon	Exon 4 of 7
AQP6	ENST00000551733.5	TSL:3	c.-139G>A	5_prime_UTR	Exon 3 of 6	ENSP00000449830.1
AQP5-AS1	ENST00000750790.1		n.178+1620C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.682

AC:

103690

AN:

151936

Hom.:

42402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.924

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.870

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.712

Gnomad FIN

AF:

0.942

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.921

Gnomad OTH

AF:

0.725

GnomAD4 exome

AF:

0.884

AC:

175

AN:

198

Hom.:

Cov.:

AF XY:

0.871

AC XY:

101

AN XY:

116

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.700

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.903

AC:

130

AN:

144

Other (OTH)

AF:

0.800

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.682

AC:

103707

AN:

152056

Hom.:

42403

Cov.:

AF XY:

0.683

AC XY:

50750

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.223

AC:

9260

AN:

41456

American (AMR)

AF:

0.673

AC:

10284

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.870

AC:

3016

AN:

3466

East Asian (EAS)

AF:

0.489

AC:

2516

AN:

5142

South Asian (SAS)

AF:

0.713

AC:

3436

AN:

4816

European-Finnish (FIN)

AF:

0.942

AC:

9983

AN:

10600

Middle Eastern (MID)

AF:

0.799

AC:

235

AN:

294

European-Non Finnish (NFE)

AF:

0.921

AC:

62613

AN:

67982

Other (OTH)

AF:

0.720

AC:

1521

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

945

1891

2836

3782

4727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<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:

0.831

Hom.:

126443

Bravo

AF:

0.643

Asia WGS

AF:

0.574

AC:

1998

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.5

(source)

DANN

Benign

0.71

PhyloP100

0.12

PromoterAI

0.0044

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over